CNS and Cardiovascular Effects of TNF-α
Recombinant cytokines have high potential for modulating immunity in cancer, viral illness and immunodeficient states. However their large use in clinical trials turned out to be impraticable because of severe systemic side-effects (Chouaib et al., 1992). The cardiovascular system and Central Nervous System (CNS) represent the main targets of Tumor Necrosis Factor (TNF-α) toxicity. Experimental studies have confirmed that systemic or intracerebral injection of recombinant TNF-α has profound cardiovascular and neurological effects in addition to its pyrogenic and metabolic activity. Understanding and elucidating the mechanisms underlying cardiovascular and CNS toxicity should enable the design of molecules to oppose this toxicity without interfering with the immune reactions.
KeywordsFatigue Migration Toxicity Depression Dehydration
Unable to display preview. Download preview PDF.
- Calapai G, Squadrito F, Massi M, Caputi AP, de Caro G (1990) Endotoxin inhibition of drinking behavior in the rat. Pharmacol Res 22: 161–170Google Scholar
- Grossman SP (ed) (1990) Thirst and Sodium appetite. Physiological basis. Academic Press San DiegoGoogle Scholar
- Kent S, Bluthe’ R, Kelley KW, Dantzer R (1992) Sickness behavior as a new target for drug development. Tips 13: 23–28.Google Scholar
- Knoweles RG, Palacios M, Plamer RM, Moncada S (1990) Kinetic characteristics of nitric oxide from rat brain. Biochem J 269: 207–210Google Scholar
- Plata-Salaman CR (1988) Food intake suppression by immunomodulators. Neurosci Res Comm 3: 159–165.Google Scholar
- Squadrito F, Calapai G, Zingarelli B, Altavilla D, Campo GM, Caputi AP (1992) Evidence for a role of nitric oxide in the endotoxin inhibition of drinking behavior in the rat. In: Moncada S, Marletta MA, Hibbs JB, Higgs RA (eds) The biology of nitric oxide I Portland Press London, 276.Google Scholar