Helen G. Durkin, PhD
Associate Professor of Pathology, Scientific Director, Center for Allergy and Asthma
Department of Pathology
Department of Medicine
Development of anti-allergy drugs and mechanisms of regulation of human and rodent IgE/allergic responses
IgE, allergy, asthma, food allergy, HIV-1, thymus, brain, magnetic stimulation, neuropeptides, Peyer's patches, bacterial cell wall components, peptidoglycan, tetracycline, minocycline, chemically modified tetracycine.
We are studying mechanisms by which tetracyclines/chemically modified tetracyclines (CMT), bacteria/bacterial cell wall components and brain/neural mechanisms regulate IgE production in rodents and in patients with allergic asthma and food allergy.
Allergic asthma and food allergies are diseases of altered IgE regulation, and are major and increasing health problems in the United States. There are no current therapies that prevent IgE production. Instead, current therapies target pathological responses after IgE is produced. More effective treatments would decrease IgE production, preventing downstream IgE-mediated effects. We found that oral tetracycline treatment of adult allergic asthmatic humans, humans with food allergies, and IgE producing rodents improves health (allergic asthmatic humans) and suppresses their ongoing IgE responses (allergic humans, rodents). We also found that tetracyclines suppress in vitro induction of specific memory IgE responses by peripheral blood mononuclear cells from ragweed sensitized allergic asthmatic patients and spleen cells from BPO-KLH sensitized mice under sterile culture conditions. Therefore, mechanisms unrelated to the antibiotic activities of these tetracyclines mediate suppression of human and murine memory IgE responses, and these mechanisms affect an epsilon specific pathway(s). We devised and prepared CMT that lack antibiotic activity, and are therefore not expected to produce the adverse effects related to long-term treatment with unmodified tetracyclines. We identified CMT lacking antibiotic activity that suppress peak ongoing rodent IgE responses and prevent in vitro induction of rodent and human specific memory IgE responses. Tetracycline and CMT mediated suppression of human and rodent IgE responses involves mechanisms that include CD1d+ monocytes and T cell-mediated pathways, especially Th2 to Th1 cytokine switching by CD4+ T cells, and suppression of CD8+CD60+ (CD45RO+) T cells and their cytokines, as well as brain, neuropeptides, and newly defined molecular pathways.
- Smith-Norowitz, TA, Silverberg, J, Norowitz, KB, Bluth, MH, Chice, S, Joks, R, Nowakowski, M, and Durkin, HG (2008). Two distinct T cell subsets, CD4+ and CD8+CD60+ and their cytokines are required for in vitro induction of human ragweed-specific memory IgE responses. J. Immunology 181: 4761-4769.
- Smith-Norowitz, TA, Drew, H, Norowitz, HM, Nowakowski, M, Bluth, EF, Durkin, HG and Bluth, MH (2008). Detection of IgE anti-parvovirus antibodies in human breast milk. Ann. Clin. Lab. Sci 38 (2) 168-173. Smith-Norowitz, TA, Durkin, HG, MH, Nowakowski, M, Bluth, MH (2008). CD8+CD60+ T cells, cells expressing epsilon specific mRNA, and Th1/Th2 cytokines in cord blood and at 7 months of age. Scandanavian Journal of Immunology 68 (5): 526-533.
- Durkin, HG and Silverberg, JI (2009). MD-PhD Careers in Translational Research. Annals of the New York Academy of Sciences, in press.
- Joks, R, Smith-Norowitz, TA, Bluth, M, Nowakowski, M, and Durkin, HG (2008). Minocycline treatment of allergic asthmatic patients and BPO-KLH sensitized mice at the peak of the hapten specific IgE response suppresses IgE, but not IgM, IgG or IgA responses. Clinical and Experimental Allergy, in press.
- Merhi, Z, Durkin, HG, Feldman, J, Macura, J, Rodriguez, C, Minkoff, H (2008). The effect of bariatric surgery on lymphocyte subtypes in women. J. Surgery for obesity and related diseases, in press.
- Yadav, K, Zehtabchi, S, Nemes, C, Miller, A, Azher, M, Durkin, HG, and Sinert, R (2008). Early immunologic responses to trauma in the Emergency Department. Emergency Medicine, in press.
- Nowakowski, M, Amassian, VE, Moshel, Y, and Durkin, HG (2006). Effect of magnetic stimulation over left temporo-parieto-occipital cortex on human blood T cell distributions and serum IgE responses. Current Topics in Neuroimmunology 15: 281-285.
- Moshel, Y, Durkin, HG, and Amassian, V (2005). Lateralized Neocortical control of T export from rat thymus: Increased export after left temporo-parieto-occipital cortical stimulation mediated by sympathetic pathways in upper spinal cord. J. Neuroimmunology,158:3-13.
- Durkln, HG and Waksman, Byron H. (2001). Thymus and tolerance. Is regulation the major function of the thymus? Immunological Reviews 182:33-57.