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Toxicologic Pathology
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Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

Jack L. Komisar

Department of Experimental Pathology, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, Jack.Komisar{at}na.amedd.Arm y.mil

Ching-Feng Weng

Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, R.O.C.

Adelekan Oyejide

Allergan, Inc, 2525 Dupont Drive, Irvine, CA 92612

Robert E. Hunt

Battelle Memorial Institute, 505 King Ave, Columbus, OH 43201

Crystal Briscoe

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground-EA, MD 21010

Jeenan Tseng

Department of Experimental Pathology, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500

Cyclosporin A (CsA), an inhibitor of T cell cytokine production, protects mice against staphylococca l enterotoxin B (SEB) intoxication. To determine whether CsA treatment would work in a species closer to humans, 4 rhesus monkeys were given 50 mg/kg CsA followed by an intratracheal challenge with approximately 6 LD50 of SEB. The CsA was not protective: one of the monkey s died and the other three had to be euthanized when they became moribund. All monkeys made IL-2, TNF, and IFN-{gamma} in response to SEB. In addition, there was about a 10-fold increase in ACTH levels 2 hr after SEB challenge. CsA significantly suppressed in vitro proliferation of lymphocytes from treated monkeys. Both CsA-treated monkeys and monkeys that had been challenged in a previous experiment with a lethal dose of SEB but had received no cyclosporin had pathologic changes in several organs. The most prominent changes were marked edema and leukocytic infiltration of the bronchial and bronchiolar mucosa. The CsA treatment appeared to reduce the intensity of lung inflammation, but this effect was not sufficient to protect the monkeys. The results suggest that CsA alone may not be an effective therapeutic agent for humans suffering from SEB intoxication or gram-positive septic shock.

Key Words: Cytokines • immunosuppression • neutrophils • shock • superantigens • T lymphocytes • toxin

Toxicologic Pathology, Vol. 29, No. 3, 369-378 (2001)
DOI: 10.1080/019262301316905336


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