Lee S. F. Soderberg

Interim Chairman/Professor, Department of Microbiology & Immunology

Immunology

Research Interest:  Immunotoxicity of drugs of abuse

Ph.D., Rutgers University

Postdoctoral , Harvard Medical School

Phone: (501) 686-6368
Fax: (501) 686-5359

E-mail

Research Description

We are studying the effects of nitrite inhalants, such as amyl, butyl, and isobutyl nitrites, on the immune system. Epidemiological studies have shown that individuals who abuse these drugs have a statistically higher probability of becoming infected with human immunodeficiency virus (HIV). In addition, AIDS patients with a history of abuse of nitrite inhalants are more likely to have Kaposi's sarcoma (KS) than are non-abuser AIDS patients. If these inhalants compromise immune mechanisms, that might suggest that abusers have reduced resistance to infection with HIV or to HHV-8, the likely etiologic agent of KS.

In my laboratory, we have developed a mouse model of inhalation exposure to study the immunotoxicity of the nitrite inhalants. Using this model, we have shown that regular exposures to isobutyl nitrite impaired three major immune mechanisms, T-dependent antibody induction, cytotoxic T cell induction, and macrophage tumoricidal activity. When mice were implanted with a syngeneic tumor, exposure to nitrite inhalants increased tumor growth by 4-fold. Intriguingly, accessory cells, macrophages and dendritic cells, appear to be the principal targets of the toxicity. We are currently investigating the effects of nitrite exposure on accessory cell functions, including the processing and presentation of tumor antigens and signal transduction pathways.

Our hypothesis is that the increase in tumor growth was caused by inhalant-induced immunosuppression, acting primarily on accessory cell functions. Looking forward, we will test the ability of the nitrite inhalants to modulate the growth of Kaposi's sarcoma and the replication of HIV and HHV-8.

References

Soderberg, L.S.F., U. Ponnappan, A. Roy, R. Schafer, and J.B. Barnett. 2004. Production of macrophage IL-1b was inhibited both at the levels of transcription and maturation by caspase-1 following inhalation exposure to isobutyl nitrite. Toxicol. Lett. 152:47-56.

Ponnappan, U., F.E. Yull, and L.S.F. Soderberg. 2004. Inhaled isobutyl nitrite inhibited macrophage inducible nitric oxide synthase by blocking NFkB signaling and promoting degradation of inducible nitric oxide synthase-2. Int. Immunopharm. 4:1075-82.

Soderberg, L.S.F., S. Boger, E.K. Fifer, and K.M. Gilbert. 2004. Macrophage production of inflammatory mediators is potently inhibited by a novel immunotherapeutic drug demonstrated to inactivate antigen-stimulated T cells. Int. Immunopharm. 4:1231-1239.

Soderberg, L.S.F. and U. Ponnappan. 2002. Cytotoxicity by nitrite inhalants is not related to peroxynitrite formation. Toxicol. Lett. 132:37-45.

Sorenson, J.R.J., L.S.F. Soderberg, L.W. Chang, and Richard Walker. 2001. Essential metalloelement chelates facilitate repair of radiation injury. Metal-Based Drugs 8:215-234.

Ponnappan, U. and L.S.F. Soderberg. 2001. Inflammatory macrophage nuclear factor-kB and proteasome activity are inhibited following inhalation exposure to inhaled isobutyl nitrite. J. Leukocyte Biol. 69:639-644.

Guo, L.G., D. Rose, J.T. Flick, J.B. Barnett and L.S.F. Soderberg. 2000. Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell responsiveness and spleen cellularity. Toxicol. Lett. 116:151-158.

Soderberg, L.S.F., A. Roy, J.T. Flick, and J.B. Barnett. 2000. Nitrite inhalants spontaneously liberate nitric oxide, which is not responsible for the immunotoxicity in C57BL/6 mice. Int. J. Immunopharmacol. 22:151-157.

Soderberg, L.S.F. 1999. Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Tox. Lett. 104:35-41.

Soderberg, L.S.F. 1998. Immunomodulation by nitrite inhalants may predispose abusers to AIDS and Kaposi’s sarcoma. J. Neuroimmunol. 83:157-161.

Soderberg, L.S.F., A. Roy, and J. B. Barnett. 1998. Isobutyl nitrite liberates nitric oxide which is not responsible for the immunotoxicity of the inhalant. Adv. Exp. Med. Biol., 437:265-268.

Soderberg, L.S.F. and J.T. Flick. 1997. Acute blood toxicity of the abused inhalant, cyclohexyl nitrite. Int. J. Immunopharmacol. 19:305-310.

Soderberg, L.S.F., L.W. Chang, and J.B. Barnett. 1996. Elevated tumor necrosis factor-a and inducible nitric oxide production by alveolar macrophages after exposure to a nitrite inhalant. J. Leukocyte Biol. 60:459-464.

Soderberg, L.S.F., J.T. Flick, and J.B. Barnett. 1996. Acute inhalation exposure to isobutyl nitrite causes nonspecific blood cell destruction. Exp. Hematol. 24:592-596.

Soderberg, L.S.F., J.T. Flick, and J.B. Barnett. 1996. Leukopenia and altered hematopoietic activity in mice exposed to the abused inhalant, isobutyl nitrite. Exp. Hematol. 24:848-853.