Interleukin biological actions

Klapproth J, Castell J, Geiger T, Andus T and Heinrich PC (1989). Fate and biological action of human recombinant interleukin ip in the rat in vivo. European Journal of Immunology, 19 1485-90. 

Interleukin-1 (IL-1) produced by monocytes and several other cell types [70, 146] has a wide array of biological properties, including T cell activation and inflammatory interactions with muscle, liver, fibroblasts, brain and bone [70, 146], IL-1, both natural and recombinant, has been shown to release histamine from human basophils and from human adenoidal mast cells [70,146,151] and this release was abolished by an IL-1 antibody. However, the average release produced by 10 units of IL-1 was less than 20% and there was considerable variability between populations of basophils in the extent of histamine release. Moreover, the secretory response elicited was quite slow (within 15 min) compared with that of other peptides [151]. Desensitization of the basophils by anti-IgE serum had no effect on the subsequent IL-1 response, suggesting different mechanisms of action [ 151], as has been the case with other peptides. Interestingly, the portion of the IL-1 molecule that is responsible for its immu-nostimulatory activity appears to be separate from that portion responsible for its proinflammatory effects [152]. However, that portion of the molecule responsible for eliciting basophil and mast-cell histamine release has not as yet been defined. 

Thalidomide (Thalomid) is a derivative of glutamic acid that is chemically related to glutethimide. It exerts a number of biological effects as an immunosuppressive, antiinflammatory, and antiangiogenic agent, yet its mechanisms of action have not been fuUy elucidated. Thalidomide potently inhibits production of tumor necrosis factor (TNF) a and interleukin (IL) 12, and its effect on these and other cytokines may account for some of its clinical effects. 

Another approach that ultimately may produce some important therapeutic results is to modulate cytokine functions. One encounters a labyrinthine maze when one views the known actions and effects of the 10 or so interleukins. First, a given cytokine has several biological functions. Furthermore, frequently any given function is mediated by two or more cytokines. Many functions provide pathological results. However, once their molecular mechanisms and biochemical pathways are understood, then decreasing the cytokine s levels or blocking its effects can produce new therapeutic modalities. Of course, their beneficial attributes can be directly exploited for therapeutic purposes. 

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