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| IL-10 INHIBITS CYTOKINE PRODUCTION, VASCULAR LEAKAGE, AND SWELLING DURING T-HELPER-1 CELL-INDUCED DELAYED-TYPE HYPERSENSITIVITY |
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| Author(s): LI L, ELLIOTT JF, MOSMANN TR |
| Source: JOURNAL OF IMMUNOLOGY Volume: 153 Issue: 9 Pages: 3967-3978 Published: NOV 1 1994 |
| Times Cited: 173 References: 57 |
| Abstract: The Th1 group of cytokines (IL-2, lFN-gamma, and lymphotoxin (LT)) is usually associated with delayed-type hypersensitivity (DTH), whereas Th2 cytokines (IL-4, IL-5, IL-6, and IL-10) often accompany Ab production. Strong DTH and Ab responses are often mutually exclusive, possibly because of negative regulation between the cytokine patterns. In vitro, IL-10 inhibits the production of cytokines by Th1 cells, and inflammatory mediators by monocytes/macrophages, suggesting that IL-10 may be a negative regulator for DTH. We have investigated the effect of systemic IL-10 on the DTH reaction (nonindurated, with edema and granulocytic infiltration) induced by injection of Th1 clones into mouse footpads. Mammalian mouse rIL-10 was purified to >90% homogeneity. The apparent in vivo half-life of i.p. injected IL-10 was approximately 2 h. Systemically administered IL-10 inhibited the 24-h footpad swelling induced by allo- and Ag-specific Th1 clones to a variable degree, with the strongest effect coinciding with peak DTH swelling. IL-10 also inhibited footpad swelling induced by a secondary challenge in SRBC-primed mice by 25 to 40%. Inhibition of Th1 induced swelling was accompanied by a similar inhibition of vascular permeability, as measured by leakage of Evans blue. Levels of IL-2, IL-6, IL-10, lFN-gamma, and TNF-alpha/LT were elevated in footpads undergoing a DTH reaction. IL-10 treatment reduced the levels of Th1 cytokines (IL-2, lFN-gamma, and TNF-alpha/LT) as well as IL-6, that was probably synthesized by other cells as a result of Th1 activation. The correlation between the inhibition of footpad swelling and cytokine production suggested that the effect of IL-10 on DTH may be mediated through suppression of cytokine synthesis. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV ALBERTA, DEPT IMMUNOL, EDMONTON T6G 2H7, AB CANADA
2. UNIV ALBERTA, DEPT MED MICROBIOL & INFECT DIS, EDMONTON T6G 2H7, AB CANADA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: PN071 |
| ISSN: 0022-1767 |
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