Pharmacological inhibition of interleukin-1 activity on T cells by hydrocortisone, cyclosporine, prostaglandins, and cyclic nucleotides.
The effects of a panel of hormones and pharmacological agents on the activation of T cells by a combination of interleukin-1 and phytohemagglutinin (IL-1/PHA) was studied. Pharmacological effects on various stages of IL-1/PHA-induced interleukin-2 (IL-2) production by the cloned murine thymoma cell line LBRM-33-1A5.7 were dissected using a multi-step assay procedure. A 4-h lag phase in the kinetics of IL-2 production allowed the operational definition of an early, IL-1-dependent programming stage, followed by an IL-2-production stage of the assay. A cell-washing procedure between these stages was introduced in order to distinguish IL-1 receptor antagonists from functional IL-1/PHA antagonists. Hydrocortisone and cyclosporine were potent inhibitors (active in the nM range) of both stages of IL-2 production, suggesting that neither is an IL-1 receptor antagonist. The cyclic adenosine monophosphate (cAMP)-elevating agents prostaglandin E2, dibutyryl cAMP, and theophylline inhibited IL-2 production during the early, IL-1-dependent programming stage. By contrast, prostaglandin F2 alpha and dibutyryl cyclic guanosine monophosphate did not appreciably inhibit IL-1/PHA activity. These results are discussed in relationship to the effects of these test agents in thymocyte IL-1 assays or mitogenesis assays and the implications toward understanding the mechanisms underlying IL-1/PHA activation of T cells.
Tracey
D E
DE
Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Hardee
M M
MM
Richard
K A
KA
Paslay
J W
JW
D000818:Animals; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D003524:Cyclosporins; D007375:Interleukin-1; D007376:Interleukin-2; D009712:Nucleotides, Cyclic; D010835:Phytohemagglutinins; D011453:Prostaglandins; D006854:Hydrocortisone