Interleukin-4 (B-cell stimulatory factor-1) augments the in vivo generation of cytotoxic cells in immunosuppressed animals.
Thymus-derived lymphocytes (T cells) are thought to play an important role in the recognition and destruction of neoplastic cells in the host. This principle has provided a foundation for the establishment of therapy with T-cell-stimulating lymphokines, notably interleukin-2, as an approach to the eradication of certain malignancies. Another lymphokine, B-cell-stimulatory factor-1 (BSF-1), also known as IL-4, has also been shown to be capable of inducing T-cell proliferation and cytolytic activity in vitro. We demonstrate herein that in immunosuppressed mice, in vivo IL-4 administration enhances the ability of treated animals to generate cytotoxic T lymphocytes directed against an allogeneic tumor challenge. Moreover, IL-4 is approximately 25 times more effective, on a weight basis, than is IL-2 in augmenting cytotoxic T-lymphocyte activity. This difference in efficiency between the two lymphokines may be partly due to the in vivo half-life. We have found that IL-4 has a serum half-life of 19 +/- 2 min following intravenous administration, in contrast to the half-life of IL-2, which has been reported to be 3.7 min +/- 0.8. These results are not only of interest for our basic understanding of the physiological role of IL-4 but may have immediate importance in clinical settings where lymphokine therapy is contemplated.
Conlon
P J
PJ
Department of Cellular Immunology, Immunex Corporation, Seattle, Washington 98101.
Tyler
S
S
Grabstein
K H
KH
Morrissey
P
P
D000818:Animals; D006801:Humans; D016867:Immunocompromised Host; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000209:etiology / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4