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Infection and Immunity, December 2005, p. 7953-7959, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7953-7959.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Increased Sensitivity to Salmonella enterica Serovar Typhimurium Infection in Mice Undergoing Withdrawal from Morphine Is Associated with Suppression of Interleukin-12

Pu Feng,1,2 Qiana M. Wilson,1,2 Joseph J. Meissler Jr,1,2 Martin W. Adler,1,3 and Toby K. Eisenstein1,2*

Center for Substance Abuse Research,1 Department of Microbiology and Immunology,2 Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 191403

Received 18 July 2005/ Accepted 23 August 2005

We have shown previously that withdrawal from morphine induces immunosuppression in mice. The present study reports the effects of morphine withdrawal on infection with Salmonella enterica serovar Typhimurium. Mice were made dependent on morphine by the implantation of a slow-release morphine pellet for 96 h. Controls received a placebo pellet. Withdrawal was induced by pellet removal. Mice were inoculated intraperitoneally with Salmonella 24 h postwithdrawal. Morphine withdrawal sensitized mice to Salmonella infection, as evidenced by increased mortality, shortened mean survival time, and increased bacterial load in the blood, spleen, and liver. Examination of the levels of a panel of proinflammatory cytokines in sera of infected, morphine-withdrawn mice showed that morphine withdrawal inhibited the elevation of interleukin-12p70 (IL-12p70). The production of IL-12p40 in morphine withdrawal mice was also suppressed. The administration of exogenous IL-12 significantly decreased the bacterial burden in morphine-withdrawn mice. These studies show a correlation between the suppression of IL-12 production and a heightened susceptibility to Salmonella infection in mice undergoing withdrawal from morphine.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140. Phone: (215) 707-3585. Fax: (215) 707-7920. E-mail: tke{at}temple.edu.

Editor: J. D. Clements

Infection and Immunity, December 2005, p. 7953-7959, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7953-7959.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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