Different pro-inflammatory profiles of interleukin 1 (IL 1) and tumor necrosis factor (TNF) in anin vivo model of inflammation

Abstract

The pro-inflammatory properties of IL 1 and TNF were investigated in an in vivo model of inflammation. IL 1 induced PMN leukocyte accumulation that was slow in onset, reaching a peak rate at 3-4 h and that was inhibitable by Actinomycin D and Cycloheximide. PMN leukocyte emigration was not associated with any significant plasma leakage. In contrast, TNF induced PMN leukocyte accumulation and oedema formation, that were rapid in onset and very short of duration (t1/2 6-10 min). TNF-induced plasma leakage was PMN leukocyte-, but not protein biosynthesis-dependent. The differences in time course and biological profile suggest that IL 1 and TNF exert their pro-inflammatory effects in vivo via different mechanisms.

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.…”

Divergent mechanisms of action of the inflammatory cytokines interleukin 1‐β and tumour necrosis factor‐α in mouse cremasteric venules

“…The involvement of locally generated proteins in these responses was investigated by using the RNA synthesis inhibitor, actinomycin D. Co‐administration of actinomycin D with the cytokines markedly suppressed leukocyte adhesion (49%) and transmigration (67%) induced by IL‐1β, but had no effect on responses elicited by TNFα. The present observations are in agreement with the findings of Rampart and colleagues who reported that the accumulation of 111 In‐neutrophils in rabbit skin in response to IL‐1β, but not TNFα, was protein synthesis dependent (Rampart & Williams, 1988; Rampart et al ., 1989b). Interestingly, using a very similar model, Cybulsky et al .…”

“…The pro‐inflammatory cytokines, IL‐1β and TNFα, have many overlapping properties and as such are often used within experimental inflammatory models interchangeably. However, a number of studies have also demonstrated key differences in the mechanisms of action of these cytokines suggesting divergence in their molecular and cellular targets (Rampart et al ., 1989b; Nathan & Sporn, 1991; Thompson et al ., 2001). The aim of the present study was to further investigate differences in the mechanisms of action of these cytokines by specifically examining the contribution of protein synthesis and the endogenously generated phospholipid mediators, PAF and LTB 4 , in different stages of leukocyte migration elicited by IL‐1β and TNFα.…”

“…No such stimulatory eects have been reported for IL-1b. In vivo, Rampart et al (1989b) demonstrated that intradermal injection of IL-1b induced a slow (maximum within 3 ± 4 h) and protein synthesis dependent neutrophil accumulation response in rabbit skin, whilst neutrophil accumulation induced by TNFa was rapid (maximum within 30 min) and protein synthesis independent. Furthermore, we have recently found that neutrophil transmigration through mouse cremasteric venules induced by IL-1b, but not TNFa, is suppressed in platelet endothelial cell adhesion molecule-1 (PECAM-1) de®cient mice (Thompson et al, 2001).…”

“…No such stimulatory effects have been reported for IL‐1β. In vivo , Rampart et al . (1989b) demonstrated that intradermal injection of IL‐1β induced a slow (maximum within 3–4 h) and protein synthesis dependent neutrophil accumulation response in rabbit skin, whilst neutrophil accumulation induced by TNFα was rapid (maximum within 30 min) and protein synthesis independent.…”