Multiple biological activities of human recombinant interleukin 1.

Abstract

Complementary DNA coding for human monocyte interleukin 1 (IL-1), pl 7 form, was expressed in Escherichia coli. During purification, IL-1 activity on murine T cells was associated with the recombinant protein. Homogeneous human recombinant IL-1 (hrIL-1) was tested in several assays to demonstrate the immunological and inflammatory properties attributed to this molecule. hrIL-1 induced proliferative responses in a cloned murine T cell in the presence of suboptimal concentrations of mitogen, whereas no effect was observed with hrIL-1 alone. At concentrations of 0.05 ng/ml, hrIL-1 doubled the response to mitogen (5 X 106 half maximal units/mg). Human peripheral blood T cells depleted of adherent cells underwent a blastogenic response and released interleukin 2 in the presence of hrIL-1 and mitogen. hrIL-1 was a potent inflammatory agent by its ability to induce human dermal fibroblast prostaglandin E2 production in vitro and to produce monophasic (endogenous pyrogen) fever when injected into rabbits or endotoxin-resistant mice. These studies establish that the dominant pl 7 form of recombinant human IL-1 possesses immunological and inflammatory properties and acts on the central nervous system to produce fever.

Induction by Toxic-Shock-Syndrome Toxin-1 of a Circulating Tumor Necrosis Factor-Like Substance in Rabbits and of Immunoreactive Tumor Necrosis Factor and Interleukin-1 from Human Mononuclear Cells

“…Using anesthetized rabbits our previous studies dem onstrated that low doses of IL-1 induce reversible hypotension and, when given as a constant infusion, a shock-like state [16]. The time course of IL-l-induced hypotension was rapid, and the onset and recovery were nearly identical to those of pyrogenic responses [24].…”

Bioactivity of skeletal muscle proteolysis-inducing factors in the plasma proteins from cancer patients with weight loss

“…Likewise, the involvement of TNF-a on catabolism of proteins has been demonstrated by some studies in vivo (Warren et al, 1987;Flores et al, 1989;Fong et al, 1989) and in vitro Charters & Grimble, 1989) and refuted in others (Kettelhutt & Goldberg, 1988;Moldawer et al, 1987;Rofe et al, 1987;Michie et al, 1988). Nevertheless, the capacity of IL-1 and TNF to cause either weight loss or anorexia in animals has often been noted (Stovroff et al, 1988;Hellestein et al, 1989;Fong et al, 1989;Michie et al, 1988; (Dinarello et al, 1986a), and polyclonal rabbit anti-sera to rhIL-1-a and rhIL-1-P (Dinarello et al, 1986b) were generously provided by Dr Charles A. Dinarello, Tufts University/New England Medical Center (Boston, MA). To neutralise IL-1 activity, the mixture of antibodies to IL-1-< and IL-1-P (final concentration of each one 0.05%) plus the serum/plasma samples were incubated at 4°C for 24 h. One control assay was carried out using rabbit nonimmune sera.…”

Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor.

“…Recombinant human IL-1-0 (112-269) had a specific activity of 5xlO 7 units/mg and was produced as described previously. 23 …”