Restriction of HIV-1 Infection in Sickle Cell Trait

Patients with Sickle cell disease (SCD) have lower risk for HIV-1 infection. We showed restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory and hemolytic factors including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs demonstrated ~2-fold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-Long Terminal Repeats (LTR) circles, HIV-1 integration and gag RNA expression. SCT PBMCs had higher HO-1 mRNA and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population level effect of SCT on HIV-1 prevalence, we assessed SCT trait among women living with HIV (WLH) in the Women Interagency HIV-1 Study (WIHS). Among WIHS African American participants, prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; OR 0.57; 95%CI = 0.36-0.92, p=0.020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow up (p=0.003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors including HO-1 and RNR2 might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.

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Interferon Induction By HbS, SERINC5 Upregulation and Reduction of HIV-1 Nef and AP2 Contribute to HIV-1 Restriction in Sickle Cell Disease

Blood ◽

10.1182/blood-2020-142699 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 5-6

Author(s):

Namita Kumari ◽

Marina Jerebtsova ◽

Songping Wang ◽

Sharmin Diaz ◽

Sergei Nekhai

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Ex Vivo ◽

Interferon Response ◽

Cell Disease ◽

Restriction Factors ◽

Peripheral Blood Mononuclear ◽

Hiv 1

Concerted action of numerous positively acting cellular factors is essential for Human immunodeficiency virus type 1 (HIV-1) replication but in turn is challenged by anti-viral restriction factors. Previously we showed that ex vivo one round HIV-1 replication and replication of fully competent T-tropic HIV-1(IIIB) is significantly reduced in peripheral blood mononuclear cells (PBMCs) obtained from patients with Sickle Cell Disease (SCD). Further, we identified and confirmed CDKN1A (p21) and CH25H as host restriction factors expressed in SCD PBMCs that may contribute to the HIV-1 inhibition, in addition to the previously reported SAMHD1 and IKBα. Since CH25H is an interferon stimulated gene (ISG), we analyzed IRFs and interferon expression in SCD PBMCs. Higher levels of IRF7 and IFNβ mRNA were observed in SCD PBMCs compared to controls. We probed further to ascertain if hemin or sickle Hb was responsible for interferon response. We found upregulation of IFNβ in THP-1 - derived macrophages treated with lysates of HbSS RBCs or purified HbS as compared to untreated or HbA treated controls. HbSS RBCs lysates and purified HbS inhibited HIV-1 gag mRNA expression in monocyte-derived macrophages infected with HIV-1(Ba-L). Recent clinical study showed increased levels of CD4 in HIV-1 infected SCD patients in Africa. Thus we analyzed CD4 levels in HIV-1 IIIB infected SCD PBMCs, and found them to be higher compared to controls. Levels of HIV-1 nef mRNA, that controls CD4 expression was lower in HIV-1 IIIB infected SCD PBMCs. As Nef counteracts SERINC3/5 restriction factor, we analyzed its expression as well as the expression of AP2 clathrin adaptor that is required for Nef mediated internalization of CD4. AP2 expression was lower and SERINC5 expression was higher in SCD PBMCs. CONCLUSIONS: SCD PBMCs could resist HIV-1 infection because of the increased IFNβ production by macrophages exposed to HbSS or sickle cell RBCs. SCD PBMC have increased levels of SERNIC5 and lower levels of HIV-1 Nef and host AP2 expression that, culumlatively, can increased CD4 levels and lead to the overall improved immunological health of SCD patients. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants (1P50HL118006, 1R01HL125005, 1SC1HL150685, 5U54MD007597, 1UM1AI26617 and P30AI087714). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosures No relevant conflicts of interest to declare.

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Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis

Mediators of Inflammation ◽

10.1155/2016/9631510 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Lingxiao Xu ◽

Qiuyue Peng ◽

Wenhua Xuan ◽

Xiaoke Feng ◽

Xiangqing Kong ◽

...

Keyword(s):

Mononuclear Cells ◽

Ex Vivo ◽

Synovial Fibroblasts ◽

Cartilage Degradation ◽

Mrna Levels ◽

Akt Signaling Pathway ◽

Peripheral Blood Mononuclear ◽

Matrix Metalloproteinase 3 ◽

Protein Levels ◽

And Cartilage

We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation whenex vivoOA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

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Restriction of HIV-1 Infection in Sickle Cell Disease Trait

Blood ◽

10.1182/blood.v130.suppl_1.940.940 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 940-940

Author(s):

Namita Kumari ◽

Javed Khan ◽

Tatiana Ammosova ◽

Asrar Ahmad ◽

Sharmin Diaz ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Ex Vivo ◽

Mrna Levels ◽

Cell Disease ◽

Intracellular Iron ◽

Cdk2 Activity ◽

Hiv 1

Abstract We recently showed that in Sickle Cell Disease (SCD), activation of anti-viral restriction factor SAMHD1 and NF-κB inhibitor, IkBα prevented ex vivo HIV-1 infection. SAMHD1 activation was due to its reduced phosphorylation by CDK2, whose activity was inhibited by reduced intracellular iron levels in SCD peripheral blood mononuclear cells (PBMC). We also found that a hazard ratio associated with HIV infection among 11,412 SCD trait subjects was 1.0% comparing to >2% HIV-1 infection among African-Americans in USA. We compared 9 HbAS HIV-1 infected individuals with 107 HbAA or HbAC HIV-1 infected individuals who were enrolled at Howard University clinic. While hemoglobin levels in these two groups were not significantly different, HIV-1 viral load was significantly lower in HbAS group as well the number of HIV-1 associated complications (Hospitalization) were reduced. In the present study, we analyzed ex vivo HIV-1 infection of SCD trait PBMC and determined the expression of iron and hypoxia-regulated host factors including HO-1, NFκB, IKK, IKBα that are implicated in HIV-1 replication. We also analyzed CDK2 activity, SAMHD1 phosphorylation and RNR2 expression in SCD trait PBMCs. One round HIV-1 infection was significantly reduced in in SCD trait PBMC. Expression of HO-1 and IKBα was upregulated in SCD trait whereas IKK and NF-κB expression was downregulated. While CDK2 activity and SAMHD1 phosphorylation were not changed, RNR2 expression was reduced. Expression levels of HIV-1 env and gag mRNA were significantly lower in HIV-1 infected SCD trait subjects. In the same patients, HO-1 and IKBα mRNA levels were upregulated comparing to HIV-1+ HbAA or HbAC subjects. Our findings suggest that HIV-1 infection might be deregulation in SCD trait and that iron metabolism and hypoxia might play a role in this deregulation. This work was supported by NIH Research Grants 1P50HL118006, 1R01HL125005, and 5G12MD007597. The content is solely the responsibility of the authors and does not necessarily represent the official view of NHLBI, NIMHD or NIH. Disclosures No relevant conflicts of interest to declare.

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Heme oxygenase-1 is induced in peripheral blood mononuclear cells of patients with acute pancreatitis: a potential therapeutic target

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00231.2010 ◽

2011 ◽

Vol 300 (1) ◽

pp. G12-G20 ◽

Cited By ~ 13

Author(s):

Aida Habtezion ◽

Raymond Kwan ◽

Alice L. Yang ◽

Maureen E. Morgan ◽

Ehsaan Akhtar ◽

...

Keyword(s):

Acute Pancreatitis ◽

Heme Oxygenase ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Ex Vivo ◽

Therapeutic Benefit ◽

Heme Oxygenase 1 ◽

Potential Therapeutic Target ◽

Peripheral Blood Mononuclear ◽

Mouse Splenocytes

Heme oxygenase-1 (HO-1) induction by hemin or Panhematin protects against experimental pancreatitis. As a preclinical first step toward determining whether HO-1 upregulation is a viable target in acute pancreatitis (AP) patients, we tested the hypothesis that HO-1 expression in peripheral blood mononuclear cell (PBMC) subsets of hospitalized patients with mild AP is upregulated then normalizes upon recovery and that cells from AP patients have the potential to upregulate their HO-1 ex vivo if exposed to Panhematin. PBMCs were isolated on days 1 and 3 of hospitalization from the blood of 18 AP patients, and PMBC HO-1 levels were compared with PMBCs of 15 hospitalized controls (HC) and 7 volunteer healthy controls (VC). On day 1 of hospitalization, AP patients compared with VCs had higher HO-1 expression in monocytes and neutrophils. Notably, AP monocyte HO-1 levels decreased significantly upon recovery. Panhematin induced HO-1 in ex vivo cultured AP PBMCs more readily than in HC or VC PBMCs. Furthermore, PBMCs from acutely ill AP patients on day 1 were more responsive to HO-1 induction compared with day 3 upon recovery. Similarly, mouse splenocytes had enhanced HO-1 inducibility as their pancreatitis progressed from mild to severe. In conclusion, AP leads to reversible PBMC HO-1 upregulation that is associated with clinical improvement and involves primarily monocytes. Leukocytes from AP patients or mice with AP are primed for HO-1 induction by Panhematin, which suggests that Panhematin could offer a therapeutic benefit.

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Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01096-08 ◽

2009 ◽

Vol 53 (5) ◽

pp. 1797-1807 ◽

Cited By ~ 54

Author(s):

Carolina Herrera ◽

Martin Cranage ◽

Ian McGowan ◽

Peter Anton ◽

Robin J. Shattock

Keyword(s):

Reverse Transcriptase ◽

Rational Design ◽

Mononuclear Cells ◽

Ex Vivo ◽

Single Point ◽

Point Mutations ◽

Peripheral Blood Mononuclear ◽

Rectal Microbicides ◽

The Individual ◽

Hiv 1

ABSTRACT We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI- and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.

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Inhibition of HIV-1 in Sickle Cell Disease Peripheral Blood Mononuclear Cells.

Blood ◽

10.1182/blood.v114.22.1509.1509 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1509-1509

Author(s):

Tatiana Ammosova ◽

Sharroya Charles ◽

Jamie Rotimi ◽

Altreisha Foster ◽

Sharmin Diaz ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Cell Disease ◽

Peripheral Blood Mononuclear ◽

Regulatory Subunits ◽

Blood Mononuclear Cells ◽

Hiv 1

Abstract Abstract 1509 Poster Board I-532 Background The hypoxic response is an important component of the body 's reaction to impaired tissue oxygenation associated with the anemia and vasoocclusive episodes of sickle cell disease (SCD). It has been reported that HIV infection progresses relatively slowly in patients with SCD (Am J Hematol 1998; 59:199-207). We recently showed that HIV-1 transcription and replication is significantly reduced in cells cultured at 3% versus 21% oxygen (J Cell Physiol 2009; in press). Our previous studies indicated that protein phosphatase-1 (PP1) interacts with HIV-1 transcriptional activator, Tat, and thereby participates in the regulation of HIV-1 transcription. Sickle cell patients are in chronically hypoxic state and we hypothesized that HIV-1 replication in their peripheral blood mononuclear cells (PBMCs) would be slower then in controls. Methods We isolated PBMCs from patients with SCD and from normal subjects, activated the cells with phytohemagglutinin and IL-2 for 24 h, and infected with pseudotyped HIV-1 virus expressing Luciferase. The infected cells were cultured at 3% of oxygen for 72 h. Results We show here that PP1 association with cellular regulatory subunits is modified and that PP1 activity is significantly reduced by 20-40% in different cell lines at 3% versus 21% oxygen. One round of replication of pseudotyped HIV-1 Luciferase virus normalized to the number of the cells in culture was significantly reduced in SCD PBMCs comparing to normal controls. Conclusions Our results provide a direct evidence of that HIV-1 replication may be slower in SCD-derived PBMCs. In future, we will analyze PP1 activity and the association of PP1 with regulatory subunits in SCD PBMCs. Understanding of how oxygen status influences HIV-1 replication might open new possibilities for treatment of hidden HIV-1 reservoirs that harbor non-replicating HIV-1 virus. Acknowledgments This work was supported by NHLBI Research Grant 2 R25 HL003679-08 from the National Institutes of Health and The Office of Research on Minority Health. Disclosures No relevant conflicts of interest to declare.

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Early ART-initiation Reduces HIV-1 Proviral DNA Levels in Children from the CHER Trial

10.21203/rs.3.rs-389348/v1 ◽

2021 ◽

Author(s):

Helen Payne ◽

Man Chan ◽

Sarah Watters ◽

Kennedy Otwombe ◽

Yuan Hsiao ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Factors Associated ◽

Proviral Dna ◽

Art Initiation ◽

Latent Hiv ◽

Dna Reduction ◽

Living With Hiv ◽

Hiv 1

Abstract BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. METHODS: Infants with HIV <12 weeks old with CD4% ≥25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40W, ART-96W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40W/ART-96W, ART was started/re-started for clinical progression or CD4% <25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression.FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p=0.0003) and 248 weeks (p=0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p=0.0225) and 248 weeks (p=0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p=0.0042).INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure.FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council.

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Function of ex vivo stimulated Natural killer T cells from patients with chronic HIV-1 infection

10.1101/831834 ◽

2019 ◽

Author(s):

Prakash Thapa ◽

Pramod Nehete ◽

Hong He ◽

Bharti Nehete ◽

Stephanie J. Buchl ◽

...

Keyword(s):

Natural Killer ◽

Peripheral Blood Mononuclear Cells ◽

Immune Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Ex Vivo ◽

Nkt Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Hiv 1

AbstractNatural killer T (NKT) cells are innate immune cells that are responsible for the first line of antiviral defense, through crosstalk with downstream antigen-presenting cells, natural killer cells, and adaptive immune cells. Previous studies have indicated that NKT cell function is severely impaired in patients with chronic HIV-1 infection. It was reported that alpha-galactosylceramide, a potent agonist antigen for NKT cells, failed to trigger the expansion of NKT cells, or the production of anti-viral cytokines by NKT cells from HIV-1 infected patients in an in vitro assay, in which peripheral blood mononuclear cells (PBMCs) were cultured in the presence of alpha-galactosylceramide. In this study, we stimulated banked peripheral blood mononuclear cells from HIV-1-infected patients with dendritic cells (DC) generated ex vivo and loaded with alpha-galactosylceramide. The results showed that NKT cells were expanded in HIV infected subjects except in patients with advanced AIDS. Expanded NKT cells were capable of producing antiviral cytokines. Our results indicate that NKT cells in HIV infected individuals are potential targets for therapeutic intervention.

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Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial

AIDS Research and Therapy ◽

10.1186/s12981-021-00389-1 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Helen Payne ◽

Man K. Chan ◽

Sarah A. Watters ◽

Kennedy Otwombe ◽

Nei-Yuan Hsiao ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Factors Associated ◽

Proviral Dna ◽

Art Initiation ◽

Latent Hiv ◽

Dna Reduction ◽

Living With Hiv ◽

Hiv 1

Abstract Background Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. Methods Infants with HIV < 12 weeks old with CD4% ≥ 25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4% < 25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥ 24 weeks ART and two consecutive undetectable HIV-1 RNA 12–24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. Findings Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p = 0.0003) and 248 weeks (p = 0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p = 0.0225) and 248 weeks (p = 0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p = 0.0042). Intepretation Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure. Funding Wellcome Trust, National Institutes of Health, Medical Research Council.

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Eosinophil Recruiting Chemokines are Down-Regulated in Peripheral Blood Mononuclear Cells of Allergic Patients Treated with Deflazocort or Desloratadine

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200702000410 ◽

2007 ◽

Vol 20 (4) ◽

pp. 745-751 ◽

Cited By ~ 2

Author(s):

M.B. Di Sciascio ◽

G. Vianale ◽

N. Verna ◽

C. Petrarca ◽

A. Perrone ◽

...

Keyword(s):

Mononuclear Cells ◽

Ex Vivo ◽

Allergic Inflammation ◽

Persistent Asthma ◽

Mrna Levels ◽

Receptor Antagonists ◽

Peripheral Blood Mononuclear ◽

Asthmatic Patients ◽

Before And After ◽

Pre Treatment

Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophil/basophil activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic/asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, 1–309 (CCL1), MCP-1 (CCL2), MIP1-α (CCL3), MIP1-β (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-α and MIP1-β with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.

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