IL-10 inhibits cytokine production, vascular leakage, and swelling during T helper 1 cell-induced delayed-type hypersensitivity.
The Th1 group of cytokines (IL-2, IFN-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, IFN-gamma, and TNF-alpha/LT were elevated in footpads undergoing a DTH reaction. IL-10 treatment reduced the levels of Th1 cytokines (IL-2, IFN-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.
Li
L
L
Department of Immunology, University of Alberta, Edmonton, Canada.
Elliott
J F
JF
Mosmann
T R
TR
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002199:Capillary Permeability / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004487:Edema / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis; D012756:Sheep / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10