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Toby K. Eisenstein, PhD

Professor, Microbiology and Immunology

Co-Director, Center for Substance Abuse Research

Telephone:  215-707- 3585

Fax:  215-707-6661

Email: tke@temple.edu

Department of Microbiology and Immunology

Center for Substance Abuse Research

Wellesley College, BA

 

Bryn Mawr College, PhD

 

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The major research areas in Dr. Eisenstein’s laboratory are investigation of the effects of opioids, cannabinoids, and alcohol, alone and in combination, on immune responses and resistance to infection. Her group has shown that all three substances suppress functional immune responses in vitro, demonstrating direct effects of these drugs on cells of the immune system. Morphine, given in vivo subacutely, suppressed antibody responses systemically and in the gastrointestinal tract. The effect of withdrawal from morphine on the immune system has been a major focus of her research, and she has shown that both abrupt and precipitated withdrawal induce profound immunosuppression through effects on macrophages and B-cells. Further, withdrawal lowers the resistance of mice to infection with Salmonella typhimurium, which correlates with failure of withdrawn mice to respond to infection with elevation in the cytokine, Interleukin-12. Her group has also found that withdrawal induces a sepsis syndrome that sensitizes mice to the lethal effects of bacterial lipopolysaccharide via increased production of tumor necrosis factor. Recently completed research examined the effect of morphine, alone and in combination with trauma, on susceptibility of mice to Acinetobacter baumannii infection and the role of IL-17A on resistance to this organism. Her laboratory is currently investigating the effect of morphine on SIV infection in monkeys as assessed by changes in functional immune assays, including natural killer cell activity, response to mitogens, and cytokine and chemokine levels. In addition, she is investigating the immunosuppressive effects of cannabinoids with activity at the CB2 receptor in inhibiting skin and organ graft rejection, and the potential of these compounds for clinical use. Further, she is examining drug interactions between cannabinoids, opioids, and alcohol in several tests of immune function.

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McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids, opioid receptors, and the immune response: a review. Drug Alcohol Depend 62(111-23)2001.

Eisenstein TK. Implications of Salmonella-induced nitric oxide (NO) for host defense and vaccines: NO, an antimicrobial, antitumor, immunosuppresive, and immunoregulatory molecule. Microbes and Infection 3:(1223-31)2001.

Eisenstein TK, Meissler JJ Jr., Geller EB, Liu-Chen L-Y, Rogers TJ, Adler MW. Nociceptin as an immunoregulatory peptide. NIDA monographs182:(97-100)2002.

Rogers TJ, Bednar F, Kaminsky DE, Davey PC, Meissler JJ Jr., Eisenstein TK. Laboratory Model Systems of Drug Abuse and their Relevance to HIV Infection and Dementia. In “The Neurology of AIDS, 2nd Ed”. ed. H. Gendelman, I. Grant, I. Everall, S. Lipton, and S. Swindells. Oxford University Press. pp. 309-320, 2005.

Eisenstein TK., Rahim RT, Feng P, Thingalaya NK, Meissler JJ. Effects of opioid tolerance and withdrawal on the immune system. J Neuroimmune Pharm 1:(237-49)2006.

Eisenstein TK, Kaminsky DE, Rahim RT, Rogers TJ.  Drugs of Abuse and the Immune System. In “NeuroImmune Pharmacology”, ed. T. Ikezu and H.   Gendelman,  Springer, NY.  (531-539).2008

Eisenstein TK, Breslow J, Song C, Finley MJ, Cornwell W, Chugh S, Meissler JJ, and Rogers TJ. 2011. “HIV and Opioids”, in “Neurology of AIDS, 3rd Ed”. ed. H. Gendelman, I. Grant, I.P. Everall, H. Glebard, H.S. Fox., S.A.Lipton, and S. Swindells. Oxford University Press. pgs. 338-353.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

23824763. Robinson RH, Meissler JJ, Breslow-Deckman JM, Gaughan J, Adler MW, Eisenstein TK, Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an In Vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction. J Neuroimmune Pharmacol :()2013 Jul 4

21826405. Breslow JM, Monroy MA, Daly JM, Meissler JJ, Gaughan J, Adler MW, Eisenstein TK, Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection. J Neuroimmune Pharmacol 6:4(551-65)2011 Dec

21627636. Eisenstein TK, Opioids and the immune system: what is their mechanism of action? Br J Pharmacol 164:7(1826-8)2011 Dec

21576323. Breslow JM, Meissler JJ Jr, Hartzell RR, Spence PB, Truant A, Gaughan J, Eisenstein TK, Innate immune responses to systemic Acinetobacter baumannii infection in mice: neutrophils, but not interleukin-17, mediate host resistance. Infect Immun 79:8(3317-27)2011 Aug

21569838. Chen X, Kirby LG, Palma J, Benamar K, Geller EB, Eisenstein TK, Adler MW, The effect of gp120 on morphine's antinociceptive and neurophysiological actions. Brain Behav Immun 25:7(1434-43)2011 Oct

20688146. Breslow JM, Feng P, Meissler JJ, Pintar JE, Gaughan J, Adler MW, Eisenstein TK, Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is µ-opioid receptor-dependent. Microb Pathog 49:6(330-5)2010 Dec

20119853. Anton B, Leff P, Meissler JJ, Calva JC, Acevedo R, Salazar A, Matus M, Flores A, Martinez M, Adler MW, Gaughan JP, Eisenstein TK, Nociceptin/orphanin FQ suppresses adaptive immune responses in vivo and at picomolar levels in vitro. J Neuroimmune Pharmacol 5:1(143-54)2010 Mar

19906780. Benamar K, Addou S, Yondorf M, Geller EB, Eisenstein TK, Adler MW, Intrahypothalamic injection of the HIV-1 envelope glycoprotein induces fever via interaction with the chemokine system. J Pharmacol Exp Ther 332:2(549-53)2010 Feb

19558543. Benamar K, Yondorf M, Geller EB, Eisenstein TK, Adler MW, Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain. Br J Pharmacol 157:7(1225-31)2009 Aug

18374539. Anton B, Leff P, Calva JC, Acevedo R, Salazar A, Matus M, Pavón L, Martinez M, Meissler JJ, Adler MW, Gaughan JP, Eisenstein TK, Endomorphin 1 and endomorphin 2 suppress in vitro antibody formation at ultra-low concentrations: anti-peptide antibodies but not opioid antagonists block the activity. Brain Behav Immun 22:6(824-32)2008 Aug

18040801. Eisenstein TK, Rahim RT, Feng P, Thingalaya NK, Meissler JJ, Effects of opioid tolerance and withdrawal on the immune system. J Neuroimmune Pharmacol 1:3(237-49)2006 Sep

17640739. Eisenstein TK, Meissler JJ, Wilson Q, Gaughan JP, Adler MW, Anandamide and Delta9-tetrahydrocannabinol directly inhibit cells of the immune system via CB2 receptors. J Neuroimmunol 189:1-2(17-22)2007 Sep

17194800. Benamar K, Yondorf M, Meissler JJ, Geller EB, Tallarida RJ, Eisenstein TK, Adler MW, A novel role of cannabinoids: implication in the fever induced by bacterial lipopolysaccharide. J Pharmacol Exp Ther 320:3(1127-33)2007 Mar

16926415. Feng P, Truant AL, Meissler JJ Jr, Gaughan JP, Adler MW, Eisenstein TK, Morphine withdrawal lowers host defense to enteric bacteria: spontaneous sepsis and increased sensitivity to oral Salmonella enterica serovar Typhimurium infection. Infect Immun 74:9(5221-6)2006 Sep

16513108. Feng P, Rahim RT, Cowan A, Liu-Chen LY, Peng X, Gaughan J, Meissler JJ Jr, Adler MW, Eisenstein TK, Effects of mu, kappa or delta opioids administered by pellet or pump on oral Salmonella infection and gastrointestinal transit. Eur J Pharmacol 534:1-3(250-7)2006 Mar 18

16299287. Feng P, Wilson QM, Meissler JJ Jr, Adler MW, Eisenstein TK, Increased sensitivity to Salmonella enterica serovar Typhimurium infection in mice undergoing withdrawal from morphine is associated with suppression of interleukin-12. Infect Immun 73:12(7953-9)2005 Dec

16204646. Rahim RT, Meissler JJ Jr, Adler MW, Eisenstein TK, Splenic macrophages and B cells mediate immunosuppression following abrupt withdrawal from morphine. J Leukoc Biol 78:6(1185-91)2005 Dec

15913793. Feng P, Meissler JJ Jr, Adler MW, Eisenstein TK, Morphine withdrawal sensitizes mice to lipopolysaccharide: elevated TNF-alpha and nitric oxide with decreased IL-12. J Neuroimmunol 164:1-2(57-65)2005 Jul

15124761. Ni X, Geller EB, Eppihimer MJ, Eisenstein TK, Adler MW, Tuma RF, Win 55212-2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model. Mult Scler 10:2(158-64)2004 Apr

14741440. Rahim RT, Feng P, Meissler JJ, Rogers TJ, Zhang L, Adler MW, Eisenstein TK, Paradoxes of immunosuppression in mouse models of withdrawal. J Neuroimmunol 147:1-2(114-20)2004 Feb

14597094. Rahim RT, Meissler JJ, Zhang L, Adler MW, Rogers TJ, Eisenstein TK, Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory molecules. J Neuroimmunol 144:1-2(16-27)2003 Nov

12044979. Rahim RT, Adler MW, Meissler JJ Jr, Cowan A, Rogers TJ, Geller EB, Eisenstein TK, Abrupt or precipitated withdrawal from morphine induces immunosuppression. J Neuroimmunol 127:1-2(88-95)2002 Jun

11755410. Eisenstein TK, Implications of Salmonella-induced nitric oxide (NO) for host defense and vaccines: NO, an antimicrobial, antitumor, immunosuppressive and immunoregulatory molecule. Microbes Infect 3:14-15(1223-31)2001 Nov-Dec

11727776. Eisenstein TK, Friedman H, The effects of drugs and neuropeptides on immunomodulation and opportunistic infection: summary of symposium 2. Adv Exp Med Biol 493:(263-4)2001

11606031. Rahim RT, Meissler JJ Jr, Cowan A, Rogers TJ, Geller EB, Gaughan J, Adler MW, Eisenstein TK, Administration of mu-, kappa- or delta2-receptor agonists via osmotic minipumps suppresses murine splenic antibody responses. Int Immunopharmacol 1:11(2001-9)2001 Oct

11564781. Peng X, Cebra JJ, Adler MW, Meissler JJ Jr, Cowan A, Feng P, Eisenstein TK, Morphine inhibits mucosal antibody responses and TGF-beta mRNA in gut-associated lymphoid tissue following oral cholera toxin in mice. J Immunol 167:7(3677-81)2001 Oct 1

11420673. Daniel R, Chung SW, Eisenstein TK, Sultzer BM, Wong PM, Specific association of Type I c-Abl with Ran GTPase in lipopolysaccharide-mediated differentiation. Oncogene 20:21(2618-25)2001 May 10

11245967. McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ, Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 62:2(111-23)2001 Apr 1

11086093. Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ, Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165:11(6519-24)2000 Dec 1

11073113. Peng X, Mosser DM, Adler MW, Rogers TJ, Meissler JJ Jr, Eisenstein TK, Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. J Leukoc Biol 68:5(723-8)2000 Nov

10964586. Ni X, Gritman KR, Eisenstein TK, Adler MW, Arfors KE, Tuma RF, Morphine attenuates leukocyte/endothelial interactions. Microvasc Res 60:2(121-30)2000 Sep

10762566. MacFarlane AS, Peng X, Meissler JJ Jr, Rogers TJ, Geller EB, Adler MW, Eisenstein TK, Morphine increases susceptibility to oral Salmonella typhimurium infection. J Infect Dis 181:4(1350-8)2000 Apr

9916105. MacFarlane AS, Schwacha MG, Eisenstein TK, In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen. Infect Immun 67:2(891-8)1999 Feb

9878455. MacFarlane AS, Huang D, Schwacha MG, Meissler JJ Jr, Gaughan JP, Eisenstein TK, Nitric oxide mediates immunosuppression induced by Listeria monocytogenes infection: quantitative studies. Microb Pathog 25:5(267-77)1998 Nov

9846819. Alicea C, Belkowski SM, Sliker JK, Zhu J, Liu-Chen LY, Eisenstein TK, Adler MW, Rogers TJ, Characterization of kappa-opioid receptor transcripts expressed by T cells and macrophages. J Neuroimmunol 91:1-2(55-62)1998 Nov 2

9826366. Schwacha MG, Meissler JJ Jr, Eisenstein TK, Salmonella typhimurium infection in mice induces nitric oxide-mediated immunosuppression through a natural killer cell-dependent pathway. Infect Immun 66:12(5862-6)1998 Dec

9666254. Eisenstein TK, Rogers TJ, Meissler JJ Jr, Adler MW, Hilburger ME, Morphine depresses macrophage numbers and function in mouse spleens. Adv Exp Med Biol 437:(33-41)1998

9666264. Guan L, Eisenstein TK, Adler MW, Rogers TJ, Modulation of DPK cell function by the kappa opioid agonist U50,488H. Adv Exp Med Biol 437:(125-36)1998

9610671. Eisenstein TK, Hilburger ME, Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations. J Neuroimmunol 83:1-2(36-44)1998 Mar 15

9607005. Eisenstein TK, Meissler JJ Jr, Miller SI, Stocker BA, Immunosuppression and nitric oxide production induced by parenteral live Salmonella vaccines do not correlate with protective capacity: a phoP::Tn10 mutant does not suppress but does protect. Vaccine 16:1(24-32)1998 Jan

9531291. Le Q, Daniel R, Chung SW, Kang AD, Eisenstein TK, Sultzer BM, Simpkins H, Wong PM, Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage activation. J Immunol 160:7(3330-6)1998 Apr 1

9413265. Hilburger ME, Adler MW, Rogers TJ, Eisenstein TK, Morphine alters macrophage and lymphocyte populations in the spleen and peritoneal cavity. J Neuroimmunol 80:1-2(106-14)1997 Dec

9393773. Schwacha MG, Eisenstein TK, Interleukin-12 is critical for induction of nitric oxide-mediated immunosuppression following vaccination of mice with attenuated Salmonella typhimurium. Infect Immun 65:12(4897-903)1997 Dec

9207365. Hilburger ME, Adler MW, Truant AL, Meissler JJ Jr, Satishchandran V, Rogers TJ, Eisenstein TK, Morphine induces sepsis in mice. J Infect Dis 176:1(183-8)1997 Jul

9143250. Guan L, Eisenstein TK, Adler MW, Rogers TJ, Inhibition of T cell superantigen responses following treatment with the kappa-opioid agonist U50,488H. J Neuroimmunol 75:1-2(163-8)1997 May

8751930. Huang D, Schwacha MG, Eisenstein TK, Attenuated Salmonella vaccine-induced suppression of murine spleen cell responses to mitogen is mediated by macrophage nitric oxide: quantitative aspects. Infect Immun 64:9(3786-92)1996 Sep

8598393. Alicea C, Belkowski S, Eisenstein TK, Adler MW, Rogers TJ, Inhibition of primary murine macrophage cytokine production in vitro following treatment with the kappa-opioid agonist U50,488H. J Neuroimmunol 64:1(83-90)1996 Jan

8531119. Eisenstein TK, Meissler JJ Jr, Rogers TJ, Geller EB, Adler MW, Mouse strain differences in immunosuppression by opioids in vitro. J Pharmacol Exp Ther 275:3(1484-9)1995 Dec

7499487. Belkowski SM, Zhu J, Liu-Chen LY, Eisenstein TK, Adler MW, Rogers TJ, Sequence of kappa-opioid receptor cDNA in the R1.1 thymoma cell line. J Neuroimmunol 62:1(113-7)1995 Oct

8535659. Eisenstein TK, Bushnell B, Meissler JJ Jr, Dalal N, Schafer R, Havas HF, Immunotherapy of a plasmacytoma with attenuated salmonella. Med Oncol 12:2(103-8)1995 Jun

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Laboratory Manager

Joseph J. Meissler

Laboratory Technician

Gieira Jones

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Jessica Breslow

Rebecca Hartzell

Certain Recent Graduates and Postdoctoral Fellows:

Jessica Breslow, Ph.D.

Postdoctoral Fellow

Department of Microbiology and Immunology

Thomas Jefferson University

Philadelphia, PA

Martin Schwacha, PhD

Tenured Professor

Department of Surgery

University of Texas Health Sciences Center at San Antonio

Pu Feng, MD, PhD

Senior Staff Scientist

Monell Research Institute

Philadelphia, PA

 

Xiaohui Peng, PhD

Research Specialist

University of Pennsylvania School of Medicine

Philadelphia, PA

 

Rahil Rahim, PhD

Director-Strategic Scientific Communications

ETHOS Health Communications

642 Newtown Yardley Road

Suite 100

Newtown, PA 18940

 

Basel Al-Ramadi, PhD

Professor and Chair

Department of Microbiology and Immunology

Faculty of Medicine and Health Sciences

United Arab Emirates University

Al Ain, UAE

 

Akshra Verma, MD, MS

Chief Medical Resident

Department of Internal Medicine

University of Illinois at Urbana-Champaign

Urbana, IL

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Current or Recent Grant Support of Active Projects:

Toby K. Eisenstein, PhD as Principal Investigator:

Temple University
Immunomodulatory Cannabinoids as Potential Therapeutics for Transplant Graft Rejection

Department of Defense (DOD) W81XWH-06-1-0147
Effect of Morphine and Trauma on Acinetobacter baumannii Infection in a Murine Model

National Institutes of Health, P01 NIDA DA023860 (Eisenstein PI of Project 4; Rogers PI of the P01)
Drugs of Abuse Affecting AIDS Pathogenesis
Project 4: Effect of Morphine and SIV on Functional Immune Responses

Toby K. Eisenstein, PhD as Co-Investigator:

National Institutes of Health, R01 DA06650, M. W. Adler, PhD, Principal Investigator
Supplement to R01 DA006650. Opioids, Cannabinoids, Chemokines: Functional Implications of Cross-Talk
Supplement is for Dr. Eisenstein to investigate the interaction of opioids, cannabinoids, and alcohol on several parameters of immune function including Mixed Lymphocyte Reaction, in vitro antibody formation, and chemotaxis.

 

National Institutes of Health, P30 DA13429, E.M. Unterwald, PhD, Principal Investigator
Center on Intersystem Regulation by Drugs of Abuse
Dr. Eisenstein is Co-Director of this Center and is Director of the Cell and Immunology Core laboratory.

 

Recent Past Funding for Toby K. Eisenstein, PhD as Principal Investigator

Commonwealth of Pennsylvania, Health Research Formula Fund Award (Tobacco Settlement Fund). Effects in Humans of Withdrawal from Opioids on Immune Status and HIV Burden

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