The antipyretic effect of polymyxin B in endotoxin-induced fever

Abstract

LPS S. typhimuPi~ (0.3~ug per kg) injected intravenously into conscious goats induced an inhibition of the extrinsic ruminal contractions in association with pyrexia and changes in heart rate. Pretreatment with polymyxin B (3 mg per kg i.v.) antagonized the endotoxin-induced symptoms in this species. In rabbits, the intravenous administration of LPS E.coli (0.I ~g per kg) resulted in a febrile response, which could be markedly reduced by pretreatment with polymyxin B. Unlike endotoxins, the febrile response to leucocytic pyrogen was not inhibited after pretreatment with this antibiotic. Moreover, polymyxin B caused only a minimal decline in the febrile response due to sodium nucleinate from yeast (|0 mg per kg). These results strengthen the view that the antipyretic activity of polymyxin B is due to an interaction of this cationic macromolecule with the anionic endotoxin molecule.

Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test

“…Detailed information can be obtained from (Cooper et al, 1972(Cooper et al, , 1979Cohen et al, 1986;Booth, 1986). In addition, drugs that influence the central or peripheral mechanisms of body temperature regulation such as antipyretic drugs, steroids, or dopamine (Cranston and luff, 1972;van Miert and van Duin, 1978;Szreder, 1997;Gagalo et al, 1995Gagalo et al, , 1996Gagalo and Matuszek, 1997;Bencsics et al, 1995;Flanigan et al, 1992;Cradock et al, 1986;Kleszynski et al, 1982) cannot be tested in the RPt. the same applies to drugs that can cause immunological reactions (e.g., immunoglobulins; Huszar et al, 2002), oily suspensions, or detergents.…”

“…One possibility for overcoming this drawback is to block the lPS signal via Polymyxin B (van Miert and van Duin, 1978;Pool et al, 1999) or CD14 antibody. Another possibility is a lAl test of the unknown substance, which normally reveals the lPS content of a sample.…”

“…It was shown (van Miert and van Duin, 1978;Pool et al, 1999) that it is possible to block lPS activity by addition of Polymyxin B, whereas Gram-positive pyrogenicity and the assay itself are unaffected. Also, in HSA samples previously positive tested by the RPt, the effect of endotoxin could be blocked by Polymyxin Each sample was incubated with whole blood with and without Polymyxin B, and the IL-1β response in the supernatant was determined by ELISA.…”

Polymyxin E-1 (colistin sulphate) (neuro-)intoxication in young ostriches ( Struthio camelus spp.)

“…Intravenous doses greater than 6 mg/kg b.wt. administered to rabbits caused acute respiratory arrest in these animals (van Miert & van Duin, 1978). dose of 35 mg/kg b.wt.…”

“…Moreover, polymyxins present antipyretic activity by binding endotoxins, especially lipid A, the active compound of lipopolysaccharide (van Miert & van Duin, 1977;Ziv et al, 1978;Warner et al, 1985;Rogers & Cohen, 1986). This property is the rationale for their application in cases of gramnegative sepsis (Hanasawa et al, 1989).…”