Detection of lymphotoxins in vivo: I. Specific identification of short-lived LT activity in the plasma of various human patients employing rabbit anti-human LT sera in vitro

Abstract

Effector molecules termed lymphokines (LK) with a broad spectrum of biologic activities are released by activated human lymphocytes in vitro. One family of LK, the lymphotoxins (LT), have been shown to be cytostatic or cytotoxic for cells in vitro. They have also been proposed to be effectors in tissue destructive cell-mediated immune reactions (CMI) in vitro. However, they have not been shown previously to be present in vivo. We tested fresh plasma from patients with rheumatoid arthritis, multiple sclerosis, and various classes of neoplasia and from recipients of allografted kidneys for LT activity. Patient plasma was cytotoxic for murine L-929 cells in vitro. Employing xenogeneic anti-human LT antisera, we were able to neutralize portions of this toxicity. This LT-like activity in patient plasma was very labile and only detectable in fresh and rapidly handled samples. Low levels of LT activity were detectable in 70 to 100% of the individuals in these patient populations. In contrast, they were completely absent in sera from healthy age-matched controls. While sera from a second type of control group, individuals with tissue destructions of nonimmunologic origin, exhibited some cytotoxic activity in vitro, only sera from one patient was significantly neutralized by anti-LT sera. The types of LT detected and the levels varied from patient group to patient group. These initial studies indicate: (a) LT-like materials exist in vivo, (b) a serum LT inactivation mechanism exists in vivo, and (c) the presence of LT in the serum may represent a new direct measure of ongoing CMI reactivity in vivo.