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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Pharmacological evidence for tumor necrosis factor as a mediator of allergic inflammation in the airways.

L M Renzetti, P M Paciorek, S A Tannu, N C Rinaldi, J E Tocker, M A Wasserman and P R Gater
Journal of Pharmacology and Experimental Therapeutics August 1996, 278 (2) 847-853;
L M Renzetti
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P M Paciorek
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S A Tannu
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N C Rinaldi
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J E Tocker
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M A Wasserman
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P R Gater
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Abstract

Tumor necrosis factor (TNF) has been implicated in the pathophysiology of a number of inflammatory diseases of the lung. Using the TNF receptor fusion protein, Ro 45-2081, our study investigated the involvement of TNF in allergic inflammatory responses in the airways of sensitized guinea pigs and Brown-Norway rats. Sensitized guinea pigs exhibited an enhanced airway reactivity to substance P (1-10 micrograms/kg, i.v.) at 6 hr after antigen challenge which was inhibited (P < .05) by Ro 45-2081 (3 mg/kg, i.p.). Treatment with Ro 45-2081 (1-3 mg/kg, i.p.) dose-dependently inhibited (P < .05) the accumulation of neutrophils and total cells in bronchoalveolar lavage fluid in sensitized guinea pigs examined at 6 and 24 hr postchallenge. Ro 45-2081 (3 mg/kg, i.p.) also significantly (P < .05) reduced the number of eosinophils in bronchoalveolar lavage at both time points whereas a lower dose (1 mg/kg, i.p.) had no effect. Ro 45-2081 (1 or 3 mg/kg, i.p.) abolished antigen-induced microvascular leakage (quantified by tissue content of Evans blue dye) in the trachea and main bronchi in sensitized guinea pigs. In the Brown-Norway rat, Ro 45-2081 (1-3 mg/kg, i.p.) caused a dose-dependent inhibition of neutrophil and eosinophil infiltration into bronchoalveolar lavage fluid at 24 hr after antigen challenge. In both guinea pig and Brown-Norway rat models, treatment with dexamethasone (30 mg/kg, i.p., for guinea pig and 0.3 mg/kg, i.p., for Brown-Norway rat) produced virtually identical results to those obtained with Ro 45-2081. The ability of Ro 45-2081 to inhibit antigen-induced responses in sensitized animals suggests that TNF is a mediator of allergic inflammation in the lung.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 278, Issue 2
1 Aug 1996
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Abstract

Pharmacological evidence for tumor necrosis factor as a mediator of allergic inflammation in the airways.

L M Renzetti, P M Paciorek, S A Tannu, N C Rinaldi, J E Tocker, M A Wasserman and P R Gater
Journal of Pharmacology and Experimental Therapeutics August 1, 1996, 278 (2) 847-853;

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Abstract

Pharmacological evidence for tumor necrosis factor as a mediator of allergic inflammation in the airways.

L M Renzetti, P M Paciorek, S A Tannu, N C Rinaldi, J E Tocker, M A Wasserman and P R Gater
Journal of Pharmacology and Experimental Therapeutics August 1, 1996, 278 (2) 847-853;
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