In vivo administration of interleukin 1 to normal mice depresses their capacity to elicit contact hypersensitivity responses: prostaglandins are involved in this modification of immune function.
The administration of pyrogenic doses of interleukin 1 (IL-1) to normal mice before contact sensitization with dinitrofluorobenzene (DNFB) resulted in a significant reduction in the intensity of the elicited contact hypersensitivity (CH) responses. Adoptive transfer experiments established no difference between normal and IL-1-pretreated mice regarding their capacity to generate splenic suppressor-cell activity and lymph node effector-cell activity in response to DNFB. However, a marked reduction in the intensity of elicited responses was observed when primed CH-effector cells, obtained from normal donors, were adoptively transferred to IL-1-pretreated recipients. This finding was paralleled by a consistent reduction in the ability of the adoptively transferred cells to infiltrate the tissue sites of antigen challenge in the IL-1-pretreated animals. Treatment of mice with indomethacin, a potent inhibitor of prostaglandin production, abrogated the capacity of IL-1 to depress CH responses following skin sensitization with DNFB. Similarly, indomethacin was also capable of abrogating the ability of IL-1 to depress CH responses of adoptive recipients of primed CH-effector cells. Our results indicate that the capacity of IL-1 to depress CH responses in normal mice is due to an indomethacin-sensitive process, presumably mediated through the IL-1-induced generation and action of prostaglandins. This was supported by our finding that treatment of mice with arachidonic acid or prostaglandin E2 caused a similar type of inhibition. The mechanism(s) responsible for this effect appears to act at the efferent level of the CH response, as evidenced by the reduced capacity of CH-effector cells to infiltrate the tissue sites of antigen challenge.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000276:immunology*; D015232:Dinoprostone; D005260:Female; D007107:Immune System / Q000187:drug effects; D007375:Interleukin-1 / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D011453:Prostaglandins / Q000502:physiology; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D007375:Interleukin-1; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D015232:Dinoprostone