Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, γ-interferon and interleukin-1

Abstract

Activated monocytes or macrophages can release soluble cytotoxic molecules capable of lysing tumour cells in vitro and thus represent an important component of the host defence mechanisms against malignancy. The recent availability of pure recombinant or natural human lymphokines and monokines and their respective polyclonal or monoclonal antibodies now makes it possible to dissect the interactions of these factors in the induction and performance of the cytotoxic event by the monocytes. Our studies indicate that pretreatment of monocytes with alpha-IFN or gamma-IFN, and also interleukin (IL)-1 or tumour necrosis factor (TNF) results in enhanced monocyte cytotoxicity. Although all these substances induce the production of IL-1 by monocytes, TNF mediates the enhanced cytotoxicity induced in monocytes by gamma-IFN, IL-1 and, in an autocrine manner, by TNF itself. Neither TNF, IL-1, gamma-IFN nor alpha-IFN mediate spontaneous monocyte cytotoxicity or that induced by alpha-IFN. Our studies thus reveal new interactions between the two monokines IL-1 and TNF and provide a dual role for TNF, as immunomodulator and mediator of monocyte cytotoxicity induced by certain specific lymphokine and monokine molecules.

TNF-α promoter polymorphisms and primary open-angle glaucoma

“…21,22 Thus, our finding that the TNF-a À308G4A and the TNF-a À238G4A polymorphisms are not associated with an increased risk for POAG does not exclude a substantial role of TNF-a in the pathogenesis of POAG, but strongly suggests that none of the investigated TNF-a gene polymorphisms is a major risk factor among Caucasian patients with POAG. Numbers for genotypes are n (%).…”

Detection of tumor necrosis factor α but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum

“…TNFa, 1L-1, and y-IFN function cooperatively to enhance monocyte-mediated cytotoxicity (14); y-IFN also acts to induce receptors for TNFa (15). Thus, the presence of both T N F a and y-IFN, as well as IL-1, in RA synovial fluid may indicate synergistic interactims between these cytokines that can contribute to the destructive inflammatory process.…”

Augmentation of recombinant interleukin‐2‐dependent murine macrophage‐mediated tumour cytotoxicity by recombinant tumour necrosis factor‐α

“…(12,13) and others (16) it seems unlikely that the TNF alone could serve as a sufficient activator of macrophage-mediated cytotoxicity against tumour cells other than the extremely TNF-sensiti ve ones. For the effective expression of such an activity an additional pre-activating or activating agent is required, such as IFN-Y (13) or IL-2 (as has been shown in this study).…”

“…TNF probably acts as an autocrine signal for macrophages to release more TNF (16). Therefore, an additional exposure to exogeneous TNF (rH-TNF) which can bind to receptors on the macrophage surface may augment TNF-dependent killing mechanisms (10).…”