Tumor necrosis factor-alpha and ultraviolet B light have similar effects on contact hypersensitivity in mice.
Acute, low dose ultraviolet B (UVB) radiation impairs the induction of dinitrofluorobenzene (DNFB)-specific contact hypersensitivity (CH) in some, but not all, inbred strains of mice. Although C3H/HeN mice are UVB-susceptible by these criteria, the closely related strain, C3H/HeJ proved to be UVB-resistant. Since the only known important genetic difference between these strains is a polymorphism at the Lps locus which governs sensitivity to bacterial lipopolysaccharide (LPS), we examined the possibility that UVB radiation achieves its immune effects via an action directly or indirectly related to LPS. We found that intradermal injections of LPS failed to impair the induction of CH when DNFB was painted at the skin injection site. However, tumor necrosis factor-alpha (TNF alpha), a cytokine released from LPS-sensitive macrophages by exposure to LPS, was able to suppress CH induction when it was injected intradermally (50 ng) prior to epicutaneous application of hapten. In addition, systemic administration of larger doses of TNF alpha (200 ng) inhibited CH, whether the cytokine was injected intraperitoneally at the time of cutaneous sensitization with DNFB, or prior to ear challenge with the hapten. Importantly, when TNF alpha was injected into pinnae of DNFB-immune mice prior to elicitation of CH, local inflammatory responses were greatly exaggerated. Thus, TNF alpha shares with acute, low dose UVB radiation the following effects on CH: impairment of induction, and amplification of expression. These effects are only achieved following local treatment with these agents. We propose that TNF alpha is an important cytokine mediator of the effects of UVB on hapten-specific CH.
Yoshikawa
T
T
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Streilein
J W
JW
D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D004139:Dinitrofluorobenzene; D005260:Female; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014466:Ultraviolet Rays
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004139:Dinitrofluorobenzene