Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.

Abstract

SummaryAlthough previous studies using human cytokines in rabbits and rats have provided evidence ofthe participation oftumor necrosis factor a (TNF-(x) and interleukin lß (IL1ß) in the meningeal inflammatory cascade, the results obtained by several groups ofinvestigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 102-10 1 IU of purified rabbit TNF-a (RaTNF-a) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant ILlß (rrIL1ß) . Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrlIrlß, anti-RaTNF-a, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 103 IU of RaTNF-a and 5 ng of rrILlß resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-a and IL1ß in the initial events of meningeal inflammation.

Toll-like receptor 3 agonist Poly I:C protects against simulated cerebral ischemia in vitro and in vivo

“…In contrast to IFNβ, TNFα, and IL-6 are important downstream products of the TLR-MyD88 pathway. TNFα and IL-6 are critically important in mediating leukocyte infiltration in tissues via the initial induction of leukocyte adhesion molecules such as vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1 and E-selection on endothelial cells [30,31] . Because TLR3 activation exclusively signals through the TRIF pathway, signaling via the TRIF-dependent pathway might serve as a neuroprotective mechanism associated with Poly I:C preconditioning in ischemia.…”

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

“…35,36,54 The contribution of TNF to tissue damage has been reported in animal studies, whereby recombinant TNF injected into the brain induced cerebral inflammation, breakdown of the BBB, and intracranial leukocyte recruitment. 55,56 Shohami et al 51 analyzed three different compounds, dexanabinol (HU-211), TNF-binding protein and pentoxifylline (PTX), for their effectiveness in inhibiting TNF transcription and bioactivity following closed head injury in rats. All three agents significantly improved neurological outcome in closed head injury animals, and administration of recombinant TNF reversed the beneficial effects.…”

IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy

“…On the other hand, IL-8 was reported not to induce neutrophil activation in heterologous systems [29][30][31], although rabbit IL-8 could induce neutrophil activation when it was injected into rabbits [13]. Thus, it is important to use homologous systems to determine the roles of cytokines in in vivo experiments as suggested by Ramilo et al [32].…”