scholarly journals Antibody and cytokine levels in visceral leishmaniasis patients with varied parasitemia before, during, and after treatment in patients admitted to Arba Minch General Hospital, southern Ethiopia

2021 ◽  
Vol 15 (8) ◽  
pp. e0009632
Author(s):  
Dagimawie Tadesse ◽  
Alemseged Abdissa ◽  
Mekidim Mekonnen ◽  
Tariku Belay ◽  
Asrat Hailu

Background Visceral leishmaniasis is a disease caused by disseminated Leishmania donovani infection which affects almost half a million people annually. Most of the patients are reported from the Indian sub-continent, Eastern Africa and Brazil. In this study, we aimed to determine the levels of antibodies and cytokines in visceral leishmaniasis patients and to examine associations of parasitemia with the clinical states of patients. A prospective study was carried out, enrolling a total of 48 active VL patients who were evaluated before, during different time points and, three months after treatment. Serum cytokine concentrations, antibody levels, parasitemia, laboratory (hematologic and biochemical) measurements, and clinical parameters were assessed. Results Counts of WBC and platelets, and measurements of hemoglobin (Hb) increased during treatment (P ≤ 0.05). Elevated levels of circulating IL-10, IFN-γ, and TGF-β1 were measured before treatment. The observed increase in serum IL-10 remarkably declined within 7 days after the start of treatment. Anti-leishmanial antibody index (AI) was high in all VL patients irrespective of spleen aspirate parasite grade before treatment and at different times during treatment. However, a significant (P ≤ 0.05) decrease of AI was observed 120 days post-treatment. IL-2 serum levels were below the detection limit at all sampling points. Conclusions The present results suggest that IL-10, IFN-γ, and TGF-β1 can be used as markers of active visceral leishmaniasis. In addition, measuring circulating cytokines concentrations, particularly IL-10, in combination with other clinical evaluations, could be used as criteria for the cure. The observation that a high serum concentration of IFN-gamma at baseline was associated with low parasitemia deserves further investigations.

2008 ◽  
Vol 76 (3) ◽  
pp. 1003-1015 ◽  
Author(s):  
Swati Bhowmick ◽  
Rajesh Ravindran ◽  
Nahid Ali

ABSTRACT Visceral leishmaniasis is deadly if not treated, and development of a vaccine with long-term immunity remains a challenge. In this study, we showed that cationic distearoyl phosphatidylcholine (DSPC) liposomes, when used as vaccine adjuvant with the immunodominant 63-kDa glycoprotein (gp63) of Leishmania donovani promastigotes, induced significant protection against progressive visceral leishmaniasis in susceptible BALB/c mice. gp63 used without adjuvant elicited partial protection but in association with liposomes exhibited marked resistance in both the livers and spleens of the mice challenged 10 days after the last vaccination. The protective efficacy of liposomal gp63 vaccination was dose dependent, with 2.5 μg of protein showing optimal protection. The immunity conferred by this vaccine formulation was durable, as mice challenged 12 weeks after immunization were still protected, and the infection was controlled for at least 3 months postchallenge. Production of gamma interferon (IFN-γ) and interleukin-4 (IL-4) by splenic T cells, and of serum immunoglobulin G1 (IgG1) and IgG2a following immunization, suggested that a mixed Th1/Th2 response had been induced following immunization. However, control of disease progression and parasitic burden in mice vaccinated with gp63 in cationic DSPC liposomes was associated with enhancement of antigen-specific IFN-γ and downregulation of IL-4, demonstrating a Th1 bias. Long-term immunity elicited by this vaccine corresponded to, in addition to the presence of antigen-specific Th1, CD8+ T-cell responses. Our results demonstrated that stable cationic liposomes containing gp63 acted as a potent adjuvant for protein antigen to induce long-term protection against L. donovani that represents an alternative to DNA vaccination.


1997 ◽  
Vol 185 (7) ◽  
pp. 1231-1240 ◽  
Author(s):  
Alice P. Taylor ◽  
Henry W. Murray

Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-γ (IFN-γ) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. This late-developing IFN-γ–independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-α (TNF-α): L. donovani infection induced TNF-α mRNA expression in parasitized GKO livers and neutralization of TNF-α reversed control at week 12. 7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-γ–independent effects. The action of IL-12 against L. donovani was TNF-α dependent and required the activity of inducible nitric oxide synthase. These results point to the presence of an IFN-γ–independent antimicrobial mechanism, mediated by TNF-α, which remains quiescent until activated late in the course of experimental visceral leishmaniasis. However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.


2011 ◽  
Vol 86 (4) ◽  
pp. 430-439 ◽  
Author(s):  
F. Tang ◽  
L. Xu ◽  
R. Yan ◽  
X. Song ◽  
X. Li

AbstractPlasmids expressing macrophage migration inhibitory factor (MIF) ofTrichinella spiralis(TsMIF), multi-cystatin-like domain protein (MCD-1) ofT. spiralis(TsMCD-1), or co-expressingTsMIF andTsMCD-1 were constructed with a pVAX1 vector. Their ability to generate a protective immune response againstT. spiralisinfection was evaluated in BALB/c mice. Groups of mice were immunized twice at 2-week intervals with 100 μg of recombinant plasmids pVAX1-Tsmif, pVAX1-Tsmcd-1or pVAX1-Tsmif-Tsmcd-1. Control animals were immunized with phosphate-buffered saline (PBS) or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant proteinTsMIF-TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17) and CD4+/CD8+T cells were monitored. Challenge infection was performed 2 weeks following the second immunization and worm burden was assayed at 35 days post-challenge. Vaccination with pVAX1-Tsmifinduced moderate serum IFN-γ and increases of CD4+and CD8+T cells, but no specific immunoglobulin antibody response. Vaccination with pVAX1-Tsmcd-1induced a predominant Th1 antibody (IgG2a and IgG2b) response and strong levels of serum IFN-γ, and increases of CD4+T cells. Importantly, co-expression ofTsMIF andTsMCD-1 in DNA immunization produced more serum IFN-γ and markedly enhanced CD4+and CD8+T cells than the single DNA vaccine of the two genes. Challenge infection demonstrated that immunization with pVAX1-Tsmif-Tsmcd-1reduced worm burdens (by 23.17%;P < 0.05).


2003 ◽  
Vol 47 (8) ◽  
pp. 2513-2517 ◽  
Author(s):  
Henry W. Murray ◽  
Elaine B. Brooks ◽  
Jennifer L. DeVecchio ◽  
Frederick P. Heinzel

ABSTRACT To determine if stimulation of Th1-cell-associated immune responses, mediated by interleukin 12 (IL-12) and gamma interferon (IFN-γ), enhance the antileishmanial effect of amphotericin B (AMB), Leishmania donovani-infected BALB/c mice were first treated with (i) exogenous IL-12 to induce IFN-γ, (ii) agonist anti-CD40 monoclonal antibody (MAb) to maintain IL-12 and induce IFN-γ, or (iii) anti-IL-10 receptor (IL-10R) MAb to blockade suppression of IL-12 and IFN-γ. In animals with established visceral infection, low-dose AMB alone (two injections of 1 mg/kg of body weight; total dose, 2 mg/kg) killed 15 to 29% of liver parasites; by themselves, the immunointerventions induced 16 to 33% killing. When the interventions were combined, the leishmanicidal activities increased 3.4-fold (anti-CD40), 6.3-fold (anti-IL-10R), and 9-fold (IL-12) compared with the activities of AMB plus the control preparations; and overall killing (76 to 84%) approximated the 84 to 92% killing effect of 7.5-fold more AMB alone (three injections of 5 mg/kg; total dose, 15 mg/kg). These results suggest that strengthening the host Th1-cell response may be a strategy for the development of AMB-sparing regimens in visceral leishmaniasis.


2021 ◽  
Vol 18 (5) ◽  
pp. 1141-1147
Author(s):  
Fang Yu ◽  
Shen Cailiang

Purpose: To investigate the effect of combination of vitamin D and anti-tuberculosis drugs on serum interleukin-1β (IL-1β), interferon-γ (IFN-γ) and helper T 17 (Th17) cell-associated cytokine levels for the treatment of spinal tuberculosis (TB). Methods: Ninety-two spinal TB patients were assigned without bias to two groups (46/group): study group (vitamin D combined with anti-TB drug group) and control group (anti-TB drug group). After treatment for 8 weeks, clinical effectiveness, adverse reactions, visual analog scale (VAS) score, spinal cord injury grade, and serum levels of IL-1β, IFN-γ, Th17, IL-10, TGF-β1, IL-17 and IL-23 were assayed with ELISA, and compared between groups. Results: Study group total effectiveness was significantly higher than that in the control group (95.65 % vs 80.43 %, p < 0.05). Before drug administration, VAS score, degree of spinal cord injury and serum levels of IL-1β, IFN-γ, IL-10, TGF-β1, IL-17 and IL-23 were comparable in the study and control patients (p > 0.05). However, post-treatment, these parameters significantly decreased in both groups (p < 0.05), but were markedly lower in study group patients, relative to controls (p < 0.05). Conclusion: The use of combined treatment of vitamin D and anti-TB drugs is an effective and safe way to alleviate inflammatory response and improve the immunity of spinal TB patients via the regulation of the levels of Th17 cell-related factors.


Author(s):  
Soraya Castro Trindade ◽  
Isaac Suzart Gomes-Filho ◽  
Simone Seixas da Cruz ◽  
Edson José Carpintero Rezende ◽  
Thiago Carôso Fróes ◽  
...  

Aims: The aim of this study was to evaluate the presence of Porphyromonas gingivalis (Pg) the in subgingival biofilm, as well as to compare the immune responses of postpartum women and their newborns to Porphyromonas gingivalis using antibody serum levels.Methods: A total of 43 postpartum women and 24 newborns were selected in the municipal maternity hospital of Alagoinhas, Bahia, Brazil between February and December 2003, for this cross-sectional study. The presence of Pg was verified using polymerase chain reaction. The immunoglobulin serum levels: IgG1, IgG2, IgG3, IgG4 and IgA, reactive to Pg ATCC33277, were tested using ELISA. Results: 39,3% of the postpartum women biofilm samples were positive for Pg. The incidence of the pathogen in the women with periodontitis (70%) was higher than in the group of women without periodontitis (30,30%). Among the newborns, high serum levels of IgG4 anti-Pg were observed (p<0.001).Conclusion: Our findings confirm that postpartum women with periodontitis present remarkable incidence of Porphyromonas gingivalis which may influence systemic response, as represented by high levels of serum antibody levels against this pathogen in women and newborns. Furthermore, evidence suggests that some antibodies crossed the placental barrier in newborns. 


2018 ◽  
Vol 17 (8) ◽  
pp. 618-625 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Sadiq Neama Al-Kufi ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes

Background & Objective: Major depressive disorder (MDD) has been associated with inflammatory processes, including increased cytokine levels, even in individuals who are otherwise physically healthy, while some MDD patients may show insulin resistance (IR). Method: However, correlations between cytokines and IR parameters have not been studied extensively in MDD. In the present study, we measured IL-1β, IL-4, IFN-γ, TGF-β1, insulin and glucose in 63 MDD patients and 27 healthy controls. The associations between cytokine levels and IR were examined. Results: The results revealed a significant increase (p<0.05) in serum levels of IL-1β, IL-4, IFN-γ, TGF-β1, insulin, insulin/glucose ratio, and insulin resistance (HOMA2IR) in MDD patients as compared with controls. There was a significant correlation between HOMA2IR with both IFN-γ (ρ=0.289, p<0.05) and TGF-β1 (ρ=0.364, p<0.05). Conclusion: The present study further confirms that MDD is accompanied by activation of the immune system with significant elevations in the levels of four cytokines. These results indicate stimulation of the immune system and increased IR and modulation of IR by increased cytokine levels in MDD. These findings show that immune activation and associated IR are a new drug target in depression.


2011 ◽  
Vol 38 (9) ◽  
pp. 1947-1952 ◽  
Author(s):  
ALESSANDRO ANTONELLI ◽  
CLODOVEO FERRI ◽  
SILVIA MARTINA FERRARI ◽  
ILARIA RUFFILLI ◽  
MICHELE COLACI ◽  
...  

Objective.No study has evaluated circulating chemokine C-X-C motif ligand (CXCL)11 in patients with “mixed cryoglobulinemia and chronic hepatitis C infection” (MC+HCV). We measured CXCL11, and correlated this measurement to the clinical phenotype.Methods.Serum CXCL11, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were assayed in 97 MC+HCV patients and in 97 sex- and age-matched controls.Results.MC+HCV patients showed significantly higher mean CXCL11 serum levels than controls (254 ± 295, 68 ± 16 pg/ml, respectively; p = 0.0002; ANOVA). CXCL11 was significantly increased in 36 cryoglobulinemic patients with compared to those without active vasculitis (303 ± 208 vs 179 ± 62 pg/ml, respectively; p < 0.001; ANOVA). IFN-γ levels were significantly higher in MC+HCV than in controls [6.1 (range 0.8–114.5), 1.4 (range 0.7–2.4) pg/ml, respectively; p < 0.05; Mann-Whitney U test]. Serum TNF-α mean levels were significantly higher in MC+HCV than in controls [13.4 (range 1.8–369), 1.1 (range 0.7–3.2) pg/ml, respectively; p < 0.0001; Mann-Whitney U test]. A multiple regression analysis considering CXCL11 as a dependent variable, and age, alanine aminotransferase, IFN-γ, and TNF-α as independent variables, showed in MC+HCV patients a significant association only with IFN-γ (p < 0.0001).Conclusion.Our study demonstrates markedly high serum levels of CXCL11 in patients with MC+HCV compared to healthy controls overall in the presence of active vasculitis. A strong relationship between circulating IFN-γ and CXCL11 was shown, strongly supporting the role of a T helper 1 immune response in the pathogenesis of MC+HCV.


2009 ◽  
Vol 51 (5) ◽  
pp. 241-246 ◽  
Author(s):  
Hiro Goto ◽  
Maria das Graças Prianti

Visceral leishmaniasis is caused by protozoan parasites of the Leishmania donovani complex. During active disease in humans, high levels of IFN-γ and TNF-α detected in blood serum, and high expression of IFN-γ mRNA in samples of the lymphoid organs suggest that the immune system is highly activated. However, studies using peripheral blood mononuclear cells have found immunosuppression specific to Leishmania antigens; this poor immune response probably results from Leishmania antigen-engaged lymphocytes being trapped in the lymphoid organs. To allow the parasites to multiply, deactivating cytokines IL-10 and TGF-β may be acting on macrophages as well as anti-Leishmania antibodies that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver and can be confirmed through the examination of organ samples. However, an analysis of sequential data from studies of visceral leishmaniasis in hamsters suggests that factors outside of the immune system are responsible for the early inactivation of inducible nitric oxide synthase, which occurs before the expression of deactivating cytokines. In active visceral leishmaniasis, the immune system actively participates in non-lymphoid organ lesioning. While current views only consider immunocomplex deposition, macrophages, T cells, cytokines, and immunoglobulins by diverse mechanism also play important roles in the pathogenesis.


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