Inflammatory properties of recombinant tumor necrosis factor in rabbit skin in vivo.

Abstract

We have investigated the ability of recombinant TNF (mouse and human) to produce acute inflammatory lesions in an established experimental model of inflammation. Upon intradermal injection in rabbit skin, TNF, in amounts as low as 3 x 10(-14) mol/site, was found to be very potent at inducing local neutrophil accumulation and neutrophil-dependent oedema formation, thereby fulfilling two important criteria to be considered as an inflammatory mediator. Our findings further indicate that the pro-inflammatory properties of TNF are probably more related to its immediate stimulatory effects on neutrophils rather than to its slow (protein biosynthesis-dependent effects on endothelial cells. Our data thus show that very low amounts of mouse and human recombinant TNF can initiate an acute inflammatory reaction in vivo in rabbit skin and that TNF is able to evoke two of the four cardinal signs of inflammation.

Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice.

“…Although our light microscopy studies indicated that the leukocytic infiltration was not massive, the ultrastructural studies clearly revealed an increase in leukocytes in transgenic versus control skin. Furthermore, our results are in agreement with a number of recombinant TNFa studies demonstrating that this factor, directly, indirectly, or synergistically, promotes chemotaxis and antimicrobial activity of neutrophils, macrophages, and eosinophils (Rothstein and Schreiber 1988;Sharpe et al 1988;Tracey et al 1988;Munro et al 1989;Rampart et al 1989).…”

“…At lower levels, TNFe~ plays an important protective role in infectious diseases, stimulating chemotaxis and the antimicrobial activity of neutrophils, macrophages, and eosinophils (Sharpe et al 1988;Tracey et al 1988;Munro et al 1989;Rampart et al 1989). That TNFoL is the mediator of these pleiotropic responses has been demonstrated by neutralizing the effects with anti-TNFa antibodies Piguet et al 1987;Tracey et al 1987;Keffer et al 1991).…”

Platelet-endothelial cell adhesion molecule-1 (PECAM-1)–deficient mice demonstrate a transient and cytokine-specific role for PECAM-1 in leukocyte migration through the perivascular basement membrane

“…47 Specifically, TNF␣-induced neutrophil accumulation was fast (maximum within 30 minutes), similar to responses induced by the chemoattractants fMLP or LTB 4 , and the response elicited by IL-1␤ was slow (maximum within 3 to 4 hours) and protein-synthesisdependent. 47,48 In summary, with the use of PECAM-1-deficient mice, the results of the present study clearly demonstrate a role for PECAM-1 as a regulatory molecule in leukocyte migration through vessel walls at sites of inflammation. However, our findings also highlight the fact that PECAM-1-independent leukocyte migration can occur in a temporal-and/or stimulusspecific manner.…”

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

“…As expected, the magnitude of LTN-induced infiltration of NK cells and T cells was greater than that of neutrophils and macrophages in control NS animals (26). In contrast, the magnitude of TNF-␣-induced infiltration of neutrophils and macrophages was greater than that of NK cells and T cells in control NS animals (27,28). Sponges were retrieved at 6, 24, 48, and 72 h after implantation.…”