Wieslaw Kozak
Georgia Regents University
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Annals of the New York Academy of Sciences | 2006
Wieslaw Kozak; Matthew J. Kluger; Johannes Tesfaigzi; Anna Kozak; Kimberly P. Mayfield; Maciej Wachulec; Karol Dokladny
Abstract: This review summarizes recent studies on endogenous antipyretic mechanisms. Fever is the result of a balance between pyrogenic and cryogenic cytokines and hormones. Although there is considerable evidence that fever evolved as a host defense response, it is important that the rise in body temperature not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified during the last 25 years. These include α‐MSH, arginine vasopressin, glucocorticoids, TNF (under certain circumstances), and IL‐10. Most recently, evidence has accumulated that cytochrome P‐450 (P‐450), part of the alternative pathway for arachidonic acid metabolism, plays an important role in reduction of fever and inflammation. Supporting a role for P‐450 in endogenous antipyresis and antiinflammation includes evidence that (1) inducers of P‐450 reduce fever, (2) inhibitors of P‐450 cause a larger fever, (3) and P‐450 arachidonic acid metabolites reduce fever.
Neuroimmunomodulation | 2001
Alexander V. Gourine; Karin Rudolph; Alla S. Korsak; Justin Kubatko; Johannes Tesfaigzi; Wieslaw Kozak; Matthew J. Kluger
Objective: Peripheral afferents play an important role in fever. In the present study, we investigated the role of capsaicin-sensitive afferents in fever and cytokine responses during systemic (induced by intraperitoneal lipopolysaccharide, LPS) and local (induced by injection of Freund’s incomplete adjuvant, FIA, into the paw) inflammation. Methods: Fevers in rats (8–10 weeks of age) whose capsaicin-sensitive afferents were depleted by neonatal capsaicin (50 mg/kg) treatment were compared to those of rats treated as neonates with vehicle. To investigate a possible involvement of cytokines, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured during LPS- and FIA-induced fever in rats after capsaicin-induced desensitization. Body temperature was measured by biotelemetry. IL-6 and TNF bioactivities in plasma were determined using bioassays. Results: The initial but not the late phase of LPS (50 µg/kg)-induced fever was markedly higher (∼1.0°C) in rats whose capsaicin-sensitive neurons were destroyed by neonatal capsaicin treatment. Capsaicin-induced desensitization also resulted in significantly higher plasma levels of IL-6 and TNF 1 but not 4 h after LPS challenge. In contrast, the day after injection with FIA (0.1 ml), rats treated with capsaicin had significantly lower body temperatures compared with vehicle-treated animals. No differences were found in plasma levels of IL-6 and TNF between capsaicin- and vehicle-treated animals in response to FIA. Conclusions: These data indicate that the role of capsaicin-sensitive afferents in fever depends on the type of inflammatory response. During systemic inflammation, capsaicin-sensitive afferents may be involved in modulating fever by regulating the levels of pyrogenic cytokines. During local inflammation, the late phase of fever is partially mediated via capsaicin-sensitive afferents.
Toxicology and Industrial Health | 2001
Rogene F. Henderson; Edward B. Barr; Walter B. Blackwell; Connie R. Clark; Carole A. Conn; Roma Kalra; Thomas H. March; Mohan L. Sopori; Yohannes Tesfaigzi; Margaret G. Ménache; Deborah C. Mash; Karol Dokladny; Wieslaw Kozak; Anna Kozak; Maceij Wachulec; Karin Rudolph; Matthew J. Kluger; Shashi P. Singh; Seddigheh Razani-Boroujerdi; Raymond J. Langley
Subclinical, repeated exposures of F344 rats to sarin resulted in brain alterations in densities of chlonergic receptor subtypes that may be associated with memory loss and cognitive dysfunction. The exposures also depressed the immune system. The rat appears to be a good model for studying the effects of subclinical exposure to a nerve gas.
Respiration Physiology | 2001
Yohannes Tesfaigzi; Matthew J. Kluger; Wieslaw Kozak
Stress stimulates the hypothalamic-pituitary-adrenal axis and leads to elevated glucocorticoid hormones (GCs). GCs reduce inflammation and suppress responses mediated by cytokines, including fever and pulmonary inflammation. Besides cyclooxygenases and lipoxygenases, cytochrome P-450 enzymes (CYP), referred to as epoxygenases, are also involved in the metabolism of arachidonic acid, implicating epoxygenases in regulating inflammation and the generation of fever. Intraperitoneal injection of lipopolysaccharide (LPS) triggers fever in rats and mice, and administration of compounds known to induce CYP reduces LPS-induced fever, while inhibitors of CYP suppress fever. Consistent with these findings, inhibitors of CYP augment the elevation of LPS-induced prostaglandin E2 levels, an endogenous pyrogen, and administration of epoxygenase metabolites results in antipyresis. CYP inducers also reduce lung inflammation, the resulting mucous cell metaplasia, and the percentage of Bcl-2-positive mucous cells in rat airways after intratracheal instillation of LPS. Together, these observations indicate that CYP modulators may have therapeutic anti-inflammatory effects, and this pathway may be involved in stress-induced reduction of inflammation.
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1994
Wieslaw Kozak; C. A. Conn; Matthew J. Kluger
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1997
Lisa R. Leon; Wieslaw Kozak; J. Peschon; Matthew J. Kluger
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1995
Wieslaw Kozak; C. A. Conn; J. J. Klir; G. H. W. Wong; Matthew J. Kluger
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1997
Matthew J. Kluger; Karin Rudolph; D. Soszynski; C. A. Conn; Lisa R. Leon; Wieslaw Kozak; Erik S. Wallen; Pope L. Moseley
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 2000
Wieslaw Kozak; Matthew J. Kluger; Anna Kozak; Maciej Wachulec; Karol Dokladny
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1997
Wieslaw Kozak; D. Soszynski; Karin Rudolph; C. A. Conn; Matthew J. Kluger