Cytokine-induced suppression and potentiation of hapten-specific immediate hypersensitivity responses.
The ability of subcutaneously (s.c.) injected cytokines (IL-4, IL-5, IL-6, IFN alpha, IFN gamma, GMCSF) to regulate the induction of hapten-specific immediate hypersensitivity (IH) responses was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten-specific IgE antibody forming cell (AFC) response. To induce IH responses, mice were injected in the right pinna with either BPO-BSA (benzylpenicilloyl-bovine serum albumin), BPO-KLH (0.01-1.0 micrograms/ml) or mcAb anti-IgE (0.001 - 1.0 micrograms/ml); and in the left pinna with an equal volume of saline (0.05 ml). Pinnae were measured 5 min to 4 hr later using a micrometer caliper. Treatment of mice with IL-4 or IFN gamma dramatically suppressed the induction of IH responses in dose dependent fashion. In contrast, treatment of mice with IL-6 and IFN alpha increased these responses in dose dependent fashion, while GMCSF and IL-5 had no effect. The suppression obtained with IL-4 and IFN gamma, and the increases seen with IL-6 and IFN alpha, were transient since these cytokines, as well as GMCSF and IL-5, had no effect on IH responses elicited 21 days after the peak of BPO-specific IgE AFC responses. The data suggest that cytokine mediated effects on IH responses occur via changes in serum levels of BPO-specific IgG1 or IgE, through direct or indirect effects of cytokines on mast cells or other cell types, or by affecting the ability of BPO-specific homocytotropic antibodies to bind to mast cell surfaces.
Auci
D L
DL
Department of Pathology, State University of New York Health Science Center, Brooklyn 11203.
Kleiner
G
G
Sheikh
A
A
Acosta
E
E
Athanassiadies
T J
TJ
Murali
M R
MR
Durkin
H G
HG
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D004431:Ear, External / Q000276:immunology / Q000473:pathology; D004487:Edema / Q000209:etiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology / Q000633:toxicity; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007279:Injections, Subcutaneous; D007372:Interferons / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D010400:Penicillin G / Q000276:immunology / Q000633:toxicity
D016207:Cytokines; D006241:Haptens; D007074:Immunoglobulin G; D007378:Interleukins; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007372:Interferons; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D010400:Penicillin G