Dissimilarities between purified human interleukin-1 and recombinant human interleukin-2 in the induction of fever, brain prostaglandin, and acute-phase protein synthesis.
The lymphokine interleukin-2 (IL-2) has been shown to enhance natural cell-mediated cytotoxicity, the generation of cytolytic T lymphocytes, and several other aspects of cellular immune function. The gene coding for human IL-2 has been cloned, and recombinant IL-2 will be available for clinical trials in patients with neoplastic, infectious, and immunodeficiency diseases. The present investigation was undertaken to determine if IL-2 was similar to interleukin-1 (IL-1) in its ability to induce fever and the acute-phase response. These studies were based on recent work with recombinant human interferon (IFN)-alpha, which is intrinsically pyrogenic and capable of producing fever by inducing the synthesis of prostaglandin E2 (PGE2). The prospect that IL-2 might exert similar physiologic effects is of critical concern since elevated temperature, PGE2, and acute-phase reactants may profoundly inhibit natural cell-mediated cytotoxicity. Our studies have shown that recombinant human IL-2 is not intrinsically pyrogenic in rabbits at doses as high as 10,000 units/kg when administered by a single intravenous injection. In contrast to IL-1, IL-2 does not stimulate cultured hypothalamus cells to synthesize PGE2, and, furthermore, IL-2 does not elevate serum C-reactive protein levels. These results predict that the administration of IL-2 to patients in doses that stimulate cellular immune function will not induce fever and other toxic side effects frequently seen in individuals receiving IFN.
D000818:Animals; D002097:C-Reactive Protein / Q000096:biosynthesis; D003001:Cloning, Molecular; D015232:Dinoprostone; D005260:Female; D005334:Fever / Q000209:etiology; D007031:Hypothalamus / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits
D007375:Interleukin-1; D007376:Interleukin-2; D011458:Prostaglandins E; D002097:C-Reactive Protein; D015232:Dinoprostone