Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1

Abstract

In vitro stimulation of mononuclear cells from human peripheral blood with mitogens causes the release of factors (monokines and lymphokines) which possess distinct biological activities. One such factor, termed 22K, can induce production of human beta-interferon (HuIFN-beta) in cultured human fibroblasts, thereby rendering these cells resistant to virus infection. Here we report the complete purification and partial sequencing (39 N-terminal amino acids) of this factor, whose relative molecular mass was estimated by SDS-polyacrylamide gel electrophoresis to be 17,000 (17K). In addition to an antiviral effect, the pure protein exhibits several other biological activities. Most significantly, intravenous (i.v.) injection of the factor in rabbits caused fever and granulopenia at doses of 0.1-1 microgram per kg, effects which we attribute to a monokine called endogenous pyrogen (EP). In vitro, the protein was scored as positive in a LAF (lymphocyte-activating factor) assay at 0.1-1 ng ml-1. LAF and EP are considered to be members of one family of monokines, called interleukin-1 (IL-1). For this reason, and also because the amino-acid sequence of the 22K factor is at least partially homologous to a complementary DNA-derived IL-1 sequence, we postulate that the 22K factor also belongs to the IL-1 family.

Interleukin‐1β and interleukin‐1α stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells

“…Human IL-1 p. This 22-kd factor was from cultures of peripheral blood mononuclear cells and was purified to homogeneity by a 4-step procedure, as previously described (20). The factor was identified as IL-1p by its N-terminal amino acid sequence (20,Zl). The material used did not contain other cytokine activities tested, including IL-1 a.…”

Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.

“…Cytokines. Natural IL-1,B (22 kD factor) was obtained from Con A-stimulated PBL and purified to homogeneity as described (9); recombinant DNA-derived IL-la, IL-1,8, and TNF-a, produced in Escherichia coli, were obtained by courtesy of Prof. C . Dinarello, Tufts University School of Medicine, Boston, MA (origin of IL-la, Genzyme Inc ., Boston, MA; origin of TNF-a, Genentech, San Francisco, CA) .…”

Induction and regulation of mRNA encoding 26-kDa protein in human cell lines treated with recombinant human tumor necrosis factor.

“…Further, the gene coding for the 26-kDa protein is also induced by a highly purified interleukin 1ip (IL-1p3)-related protein obtained from con A-stimulated human leukocytes (5), later demonstrated to be identical to IL-1f3 (6). Although it has been claimed that the 26-kDa protein has a weak IFN-like activity-neutralized by anti-IFN-p8 sera-the biological function of this molecule remained mysterious until the recent report of an identical cDNA sequence coding for an interleukin, active on Blymphocytes (7)(8)(9), and having a potent growth factor activity on the same cells (10).…”