Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis

AIM: To investigate the potential interactions of thymic stromal lymphopoietin (TSLP) with interleukin-4 (IL-4) in adaptive immunity during fungal keratitis (FK). METHODS: An FK mouse model was induced with Aspergillus fumigatus (AF) hyphal infection. Mice were divided into several groups: untreated, phosphate buffer saline (PBS), infected with AF, and pretreated with a scrambled siRNA, a TSLP-specific siRNA (TSLP siRNA), murine recombinant TSLP (rTSLP), immunoglobulin G (IgG), murine recombinant IFN (rIFN-γ), murine recombinant IL-4 (rIL-4), rIL-13, murine recombinant IL-17A (rIL-17A), and murine recombinant IL-17F (rIL-17F) groups. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) or Western blot were performed to determine mRNA and protein levels in the inflamed cornea. Cytokine locations were observed by immunofluoresence staining after AF hyphal infection. RESULTS: Compared to those in the untreated group, TSLP and T helper type 1 (Th1) cytokine levels in the AF group were upregulated at 24h post infection (hpi), and those of T helper type 2 (Th2) and T helper type 17 (Th17) cytokines were increased at 5d post infection (dpi). Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group. The TSLP level was increased in the rIL-4-pretreated group, but there were no significant changes among the other groups. Immunofluorescence staining showed cytokine locations after AF hyphal infection. CONCLUSION: TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo. IL-4 promotes TSLP secretion. Therefore, TSLP with IL-4 regulates adaptive immunity in FK.

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Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer

The Journal of Laryngology & Otology ◽

10.1017/s0022215106002428 ◽

2006 ◽

Vol 121 (3) ◽

pp. 246-252 ◽

Cited By ~ 48

Author(s):

A Jebreel ◽

D Mistry ◽

D Loke ◽

G Dunn ◽

V Hough ◽

...

Keyword(s):

Head And Neck ◽

Tumour Response ◽

Interleukin 10 ◽

Th2 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tumour Stage ◽

T Helper ◽

Serum Cytokine ◽

Cytokine Levels ◽

Helper Type

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract.Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response.The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined.Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay.The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2–61.6 vs 52.3 pg/ml, 37.5–113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169).These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.

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Glucocorticoids Inhibit Proliferation and Interleukin-4 and Interleukin-5 Secretion by Aeroallergen-Specific T-Helper Type 2 Cell Lines

Annals of Allergy Asthma & Immunology ◽

10.1016/s1081-1206(10)63075-x ◽

1998 ◽

Vol 80 (6) ◽

pp. 509-516 ◽

Cited By ~ 28

Author(s):

I Caroline Crocker ◽

Martin K Church ◽

Sean Newton ◽

Robert G Townley

Keyword(s):

Cell Lines ◽

Interleukin 4 ◽

T Helper ◽

Interleukin 5 ◽

Helper Type

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Two signals are involved in polyclonal B cell stimulation by T helper type 2 cells: a role for LFA-1 molecules and interleukin 4

European Journal of Immunology ◽

10.1002/eji.1830220246 ◽

1992 ◽

Vol 22 (2) ◽

pp. 599-602 ◽

Cited By ~ 7

Author(s):

Michael Lohoff ◽

Andreas Koch ◽

Martin Röllinghoff

Keyword(s):

B Cell ◽

Interleukin 4 ◽

T Helper ◽

Cell Stimulation ◽

Helper Type

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Two distinct non-T helper type 2 interleukin-4 cell subsets in mice as revealed by single-cell cytokine analysis

European Journal of Immunology ◽

10.1002/eji.1830240309 ◽

1994 ◽

Vol 24 (3) ◽

pp. 549-557 ◽

Cited By ~ 9

Author(s):

Ilona Kariv ◽

Richard R. Hardy ◽

Kyoko Hayakawa

Keyword(s):

Single Cell ◽

Interleukin 4 ◽

T Helper ◽

Cytokine Analysis ◽

Helper Type

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Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.

Journal of Experimental Medicine ◽

10.1084/jem.177.6.1797 ◽

1993 ◽

Vol 177 (6) ◽

pp. 1797-1802 ◽

Cited By ~ 428

Author(s):

J P Sypek ◽

C L Chung ◽

S E Mayor ◽

J M Subramanyam ◽

S J Goldman ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

Enzyme Linked Immunosorbent Assay ◽

Th1 Cells ◽

T Helper ◽

Ifn Gamma ◽

Lymph Node Cells ◽

Helper Type

Resistance to Leishmania major in mice is associated with the appearance of distinct T helper type 1 (Th1) and Th2 subsets. T cells from lymph nodes draining cutaneous lesions of resistant mice are primarily interferon gamma (IFN-gamma)-producing Th1 cells. In contrast, T cells from susceptible mice are principally Th2 cells that generate interleukin 4 (IL-4). Although existing evidence is supportive of a role for IFN-gamma in the generation of Th1 cells, additional factors may be required for a protective response to be maintained. A potential candidate is IL-12, a heterodimeric cytokine produced by monocytes and B cells that has multiple effects on T and natural killer cell function, including inducing IFN-gamma production. Using an experimental leishmanial model we have observed that daily intraperitoneal administration at the time of parasite challenge of either 0.33 micrograms IL-12 (a consecutive 5 d/wk for 5 wk) or 1.0 micrograms IL-12 per mouse (only a consecutive 5 d) caused a > 75% reduction in parasite burden at the site of infection, in highly susceptible BALB/c mice. Delay of treatment by 1 wk had less of a protective effect. Concomitant with these protective effects was an increase in IFN-gamma and a decrease in IL-4 production, as measured by enzyme-linked immunosorbent assay of supernatants generated from popliteal lymph node cells stimulated with leishmanial antigen in vitro. The reduction in parasite numbers induced by IL-12 therapy was still apparent at 10 wk postinfection. In addition, we observed that the administration of a rabbit anti-recombinant murine IL-12 polyclonal antibody (200 micrograms i.p. every other day for 25 d) at the time of infection to resistant C57Bl/6 mice exacerbated disease. These effects were accompanied by a shift in IFN-gamma production in vitro by antigen-stimulated lymph node cells indicative of a Th2-like response. These findings suggest that IL-12 has an important role in initiating a Th1 response and protective immunity.

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