CLARK M. BLATTEIS, Ph.D., M.Sc., B.A.

Distinguished Professor
Physiology

Office: S305 VAN VLEET CANCER CENTER
3 NORTH DUNLAP STREET
MEMPHIS TN 381632113
Tel: (901) 448-5845
cblattei@uthsc.edu

Education

  • M.S., University of Iowa, Iowa City, Iowa
  • B.A.,

Research description

Fever is one among an array of non-specific innate immune, endocrine, metabolic, behavioral, and other responses to the entry into the body of infectious microorganisms or their products, designed to defend the afflicted host from the deleterious effects of the invading pathogens. These responses are collectively termed the acute-phase reaction (APR). The APR is thus a physiological, not a pathological, response. In its simplest terms, the febrile response per se is characterized by a rise of the body core temperature (Tc). It is, thus, a thermoregulatory response that involves a complete, prototypic reflex arc ? sensory signaling, central integration, and effector mechanisms. Over the years, we have, in turn, described the ontogeny of fever and the change in effector mechanisms that occurs over the first month of post-natal life, localized the several brain sites that mediate the febrile response, and eventually characterized the complete loop of fever production, from the moment the pyrogenic material enters the body until the febrile response is initiated. In more recent years, our efforts have been concentrated most heavily on resolving this latter issue. Thus, we have identified various endogenous factors liberated in immediate response to the presence of a pyrogen and the neural and humoral pathways activated that ultimately communicate these signals to the brain. In the course of these studies, we have uncovered several fever-triggering processes and delineated the trajectories of their pathways from the periphery to the brain. We have also described the neurochemical processes in the brain for febrigenesis, and developed a conceptual model of the afferent and central mechanisms involved. These are depicted in the diagram.

Research interest/specialty

Our lab has been principally engaged in elucidating the mechanisms that underlie the febrile response to infection. The focus of our research has been on the interactions between the immune and nervous systems that initiate this response.

Research keywords

endotoxic fever production, febrile response, infection,

Research interest/specialty

Our lab has been principally engaged in elucidating the mechanisms that underlie the febrile response to infection. The focus of our research has been on the interactions between the immune and nervous systems that initiate this response.

Research keywords

endotoxic fever production, febrile response, infection,

Research description

Fever is one among an array of non-specific innate immune, endocrine, metabolic, behavioral, and other responses to the entry into the body of infectious microorganisms or their products, designed to defend the afflicted host from the deleterious effects of the invading pathogens. These responses are collectively termed the acute-phase reaction (APR). The APR is thus a physiological, not a pathological, response. In its simplest terms, the febrile response per se is characterized by a rise of the body core temperature (Tc). It is, thus, a thermoregulatory response that involves a complete, prototypic reflex arc ? sensory signaling, central integration, and effector mechanisms. Over the years, we have, in turn, described the ontogeny of fever and the change in effector mechanisms that occurs over the first month of post-natal life, localized the several brain sites that mediate the febrile response, and eventually characterized the complete loop of fever production, from the moment the pyrogenic material enters the body until the febrile response is initiated. In more recent years, our efforts have been concentrated most heavily on resolving this latter issue. Thus, we have identified various endogenous factors liberated in immediate response to the presence of a pyrogen and the neural and humoral pathways activated that ultimately communicate these signals to the brain. In the course of these studies, we have uncovered several fever-triggering processes and delineated the trajectories of their pathways from the periphery to the brain. We have also described the neurochemical processes in the brain for febrigenesis, and developed a conceptual model of the afferent and central mechanisms involved. These are depicted in the diagram.

Publications

  1. Li, S, Dou, W, Tang, Y, Goorha, S, Ballou, LR, Blatteis, CM. Acetaminophen: antipyretic or hypothermic in mice? In either case, PGHS-1b (COX-3) is irrelevant. Prostaglandins Other Lipid Mediat, 85 (3-4), 89-99, 2008.
  2. Feleder, C, Perlik, V, Blatteis, CM. Preoptic nitric oxide attenuates endotoxic fever in guinea pigs by inhibiting the POA release of norepinephrine. Am J Physiol Regul Integr Comp Physiol, 293 (3), R1144-51, 2007.
  3. Feleder, C, Perlik, V, Blatteis, CM. Preoptic norepinephrine mediates the febrile response of guinea pigs to lipopolysaccharide. Am J Physiol Regul Integr Comp Physiol, 293 (3), R1135-43, 2007.
  4. Blatteis, CM. The onset of fever: new insights into its mechanism. Prog Brain Res, 162, 3-14, 2007.
  5. Blatteis, CM. Endotoxic fever: new concepts of its regulation suggest new approaches to its management. Pharmacol Ther, 111 (1), 194-223, 2006.
  6. Li, Z, Perlik, V, Feleder, C, Tang, Y, Blatteis, CM. Kupffer cell-generated PGE2 triggers the febrile response of guinea pigs to intravenously injected LPS. Am J Physiol Regul Integr Comp Physiol, 290 (5), R1262-70, 2006.
  7. Feleder, C, Perlik, V, Tang, Y, Blatteis, CM. Putative antihyperpyretic factor induced by LPS in spleen of guinea pigs. Am J Physiol Regul Integr Comp Physiol, 289 (3), R680-7, 2005.
  8. Perlik, V, Li, Z, Goorha, S, Ballou, LR, Blatteis, CM. LPS-activated complement, not LPS per se, triggers the early release of PGE2 by Kupffer cells. Am J Physiol Regul Integr Comp Physiol, 289 (2), R332-R339, 2005.
  9. Blatteis, CM, Li, S, Li, Z, Feleder, C, Perlik, V. Cytokines, PGE2 and endotoxic fever: a re-assessment. Prostaglandins Other Lipid Mediat, 76 (1-4), 1-18, 2005.
  10. Li, Z, Feleder, C, Blatteis, CM. Lipopolysaccharide challenge causes exaggerated fever and increased hepatic lipopolysaccharide uptake in vinblastine-induced leukopenic guinea pigs. Crit Care Med, 32 (10), 2131-4, 2004.
  11. Feleder, C, Perlik, V, Blatteis, CM. Preoptic alpha 1- and alpha 2-noradrenergic agonists induce, respectively, PGE2-independent and PGE2-dependent hyperthermic responses in guinea pigs. Am J Physiol Regul Integr Comp Physiol, 286 (6), R1156-66, 2004.
  12. Li, Z, Blatteis, CM. Fever onset is linked to the appearance of lipopolysaccharide in the liver. J Endotoxin Res, 10 (1), 39-53, 2004.
  13. Li, S, Boackle, SA, Holers, VM, Lambris, JD, Blatteis, CM. Complement component c5a is integral to the febrile response of mice to lipopolysaccharide. Neuroimmunomodulation, 12 (2), 67-80, 2004.
  14. Blatteis, CM, Li, S, Li, Z, Perlik, V, Feleder, C. Signaling the brain in systemic inflammation: the role of complement. Front Biosci, 9, 915-31, 2004.
  15. Li, S, Goorha, S, Ballou, LR, Blatteis, CM. Intracerebroventricular interleukin-6, macrophage inflammatory protein-1 beta and IL-18: pyrogenic and PGE(2)-mediated. Brain Res, 992 (1), 76-84, 2003.
  16. Feleder, C, Li, Z, Perlik, V, Evans, A, Blatteis, CM. The spleen modulates the febrile response of guinea pigs to LPS. Am J Physiol Regul Integr Comp Physiol, 284 (6), R1466-76, 2003.
  17. Li, S, Llanos-Q, J, Blatteis, CM. Thermal response to zymosan: the differential role of complement. Neuroimmunomodulation, 10 (2), 122-8, 2002.
  18. Li, S, Holers, VM, Boackle, SA, Blatteis, CM. Modulation of mouse endotoxic fever by complement. Infect Immun, 70 (5), 2519-25, 2002.
  19. Steiner, AA, Li, S, Llanos-Q, J, Blatteis, CM. Differential inhibition by nimesulide of the early and late phases of intravenous- and intracerebroventricular-LPS-induced fever in guinea pigs. Neuroimmunomodulation, 9 (5), 263-75, 2002.
  20. Li, S, Ballou, LR, Morham, SG, Blatteis, CM. Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta. Brain Res, 910 (1-2), 163-73, 2001.
  21. Blatteis, CM, Li, S. Pyrogenic signaling via vagal afferents: what stimulates their receptors. Auton Neurosci, 85 (1-3), 66-71, 2000.
  22. Blatteis, CM, Sehic, E, Li, S. Pyrogen sensing and signaling: old views and new concepts. Clin Infect Dis, 31 Suppl 5, S168-77, 2000.
  23. Blatteis, CM. The afferent signalling of fever. J Physiol, 526 Pt 3, 470, 2000.
  24. Blatteis, CM. Thermoregulation in complex situations: combined heat exposure, infectious fever and water deprivation. Int J Biometeorol, 44 (1), 31-43, 2000.
  25. Blatteis, CM, Sehic, E, Li, S. Complement and the pathogenesis of endotoxic fever. Int J Biometeorol, 43 (4), 176-83, 2000.
  26. Li, S, Sehic, E, Wang, Y, Ungar, AL, Blatteis, CM. Relation between complement and the febrile response of guinea pigs to systemic endotoxin. Am J Physiol, 277 (6 Pt 2), R1635-45, 1999.
  27. Li, S, Wang, Y, Matsumura, K, Ballou, LR, Morham, SG, Blatteis, CM. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(-/-), but not in cyclooxygenase-1(-/-) mice. Brain Res, 825 (1-2), 86-94, 1999.
  28. Blatteis, CM, Sehic, E, Li, S. Afferent pathways of pyrogen signaling. Ann N Y Acad Sci, 856, 95-107, 1998.
  29. Sehic, E, Li, S, Ungar, AL, Blatteis, CM. Complement reduction impairs the febrile response of guinea pigs to endotoxin. Am J Physiol, 274 (6 Pt 2), R1594-603, 1998.
  30. Blatteis, CM, Sehic, E. Cytokines and fever. Ann N Y Acad Sci, 840, 608-18, 1998.
  31. Sehic, E, Hunter, WS, Ungar, AL, Blatteis, CM. Blockade of Kupffer cells prevents the febrile and preoptic prostaglandin E2 responses to intravenous lipopolysaccharide in guinea pigs. Ann N Y Acad Sci, 813, 448-52, 1997.
  32. Blatteis, CM, Fregly, MS. Melvin J. Fregly. A tribute. Ann N Y Acad Sci, 813, xviii, 1-4, 1997.
  33. Romanovsky, AA, Blatteis, CM. Naltrexone modifies thermoregulatory symptoms and lessens the severity of heat stroke in guinea pigs. Ann N Y Acad Sci, 813, 548-52, 1997.
  34. Tague, LL, Blatteis, CM. Thermophysiology in cyberspace. Time- and location-independent interative research information URL http://physiol.utmem.edu/thermophysiology/. Ann N Y Acad Sci, 813, 216-24, 1997.
  35. Blatteis, CM, Sehic, E. Circulating pyrogen signaling of the brain. A new working hypothesis. Ann N Y Acad Sci, 813, 445-7, 1997.
  36. Sehic, E, Gerstberger, R, Blatteis, CM. The effect of intravenous lipopolysaccharide on NADPH-diaphorase staining (= nitric oxide synthase activity) in the organum vasculosum laminae terminalis of guinea pigs. Ann N Y Acad Sci, 813, 383-91, 1997.
  37. Oladehin, A, Blatteis, CM. Induction of Fos protein in neonatal rat hypothalami following intraperitoneal endotoxin injection. Ann N Y Acad Sci, 813, 480-4, 1997.
  38. Romanovsky, AA, Blatteis, CM. Heat stroke: opioid-mediated mechanisms. J Appl Physiol, 81 (6), 2565-70, 1996.
  39. Sehic, E, Ungar, AL, Blatteis, CM. Interaction between norepinephrine and prostaglandin E2 in the preoptic area of guinea pigs. Am J Physiol, 271 (3 Pt 2), R528-36, 1996.
  40. Sehic, E, Blatteis, CM. Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs. Brain Res, 726 (1-2), 160-6, 1996.
  41. Sehic, E, Székely, M, Ungar, AL, Oladehin, A, Blatteis, CM. Hypothalamic prostaglandin E2 during lipopolysaccharide-induced fever in guinea pigs. Brain Res Bull, 39 (6), 391-9, 1996.
  42. Oladehin, A, Blatteis, CM. Lipopolysaccharide-induced Fos expression in hypothalamic nuclei of neonatal rats. Neuroimmunomodulation, 2 (5), 282-9, 1995.
  43. Romanovsky, AA, Blatteis, CM. Biphasic fever: what triggers the second temperature rise. Am J Physiol, 269 (2 Pt 2), R280-6, 1995.
  44. Blatteis, CM, Xin, L, Quan, N. Neuromodulation of fever. A possible role for substance P. Ann N Y Acad Sci, 741, 162-73, 1994.
  45. Romanovsky, AA, Shido, O, Ungar, AL, Blatteis, CM. Peripheral naloxone attenuates lipopolysaccharide fever in guinea pigs by an action outside the blood-brain barrier. Am J Physiol, 266 (6 Pt 2), R1824-31, 1994.
  46. Shido, O, Romanovsky, AA, Ungar, AL, Blatteis, CM. Role of intrapreoptic norepinephrine in endotoxin-induced fever in guinea pigs. Am J Physiol, 265 (6 Pt 2), R1369-75, 1993.
  47. Romanovsky, AA, Shido, O, Ungar, AL, Blatteis, CM. Genesis of biphasic thermal response to intrapreoptically microinjected clonidine. Brain Res Bull, 31 (5), 509-13, 1993.
  48. Xin, L, Blatteis, CM. Hypothalamic neuronal responses to interleukin-6 in tissue slices: effects of indomethacin and naloxone. Brain Res Bull, 29 (1), 27-35, 1992.
  49. Quan, N, Xin, L, Ungar, AL, Hunter, WS, Blatteis, CM. Validation of the hypothermic action of preoptic norepinephrine in guinea pigs. Brain Res Bull, 28 (4), 537-42, 1992.
  50. Quan, N, Xin, L, Ungar, AL, Blatteis, CM. Preoptic norepinephrine-induced hypothermia is mediated by alpha 2-adrenoceptors. Am J Physiol, 262 (3 Pt 2), R407-11, 1992.
  51. Xin, L, Blatteis, CM. Blockade by interleukin-1 receptor antagonist of IL-1 beta-induced neuronal activity in guinea pig preoptic area slices. Brain Res, 569 (2), 348-52, 1992.
  52. Blatteis, CM. Role of the OVLT in the febrile response to circulating pyrogens. Prog Brain Res, 91, 409-12, 1992.
  53. Shibata, M, Blatteis, CM. Differential effects of cytokines on thermosensitive neurons in guinea pig preoptic area slices. Am J Physiol, 261 (5 Pt 2), R1096-103, 1991.
  54. Shibata, M, Blatteis, CM. Human recombinant tumor necrosis factor and interferon affect the activity of neurons in the organum vasculosum laminae terminalis. Brain Res, 562 (2), 323-6, 1991.
  55. Quan, N, Xin, L, Blatteis, CM. Microdialysis of norepinephrine into preoptic area of guinea pigs: characteristics of hypothermic effect. Am J Physiol, 261 (2 Pt 2), R378-85, 1991.
  56. Shibata, M, Blatteis, CM. High perfusate PO2 impairs thermosensitivity of hypothalamic thermosensitive neurons in slice preparations. Brain Res Bull, 26 (3), 467-71, 1991.
  57. Blatteis, CM, Xin, L, Quan, N. Neuromodulation of fever: apparent involvement of opioids. Brain Res Bull, 26 (2), 219-23, 1991.
  58. Blatteis, CM, Quan, N, Xin, L, Ungar, AL. Neuromodulation of acute-phase responses to interleukin-6 in guinea pigs. Brain Res Bull, 25 (6), 895-901, 1990.
  59. Shibata, M, Blatteis, CM. Lack of mimicry between the effects of pyrogenic cytokines and monoamines on the activities of hypothalamic thermosensitive neurons. Int J Neurosci, 51 (3-4), 291-3, 1990.
  60. Blatteis, CM. Neuromodulative actions of cytokines. Yale J Biol Med, 63 (2), 133-46, 1990.
  61. Quan, N, Blatteis, CM. Intrapreoptically microdialyzed and microinjected norepinephrine evokes different thermal responses. Am J Physiol, 257 (4 Pt 2), R816-21, 1989.
  62. Quan, N, Blatteis, CM. Microdialysis: a system for localized drug delivery into the brain. Brain Res Bull, 22 (4), 621-5, 1989.
  63. Shoham, S, Blatteis, CM, Krueger, JM. Effects of preoptic area lesions on muramyl dipeptide-induced sleep and fever. Brain Res, 476 (2), 396-9, 1989.
  64. Krueger, JM, Majde, JA, Blatteis, CM, Endsley, J, Ahokas, RA, Cady, AB. Polyriboinosinic:polyribocytidylic acid enhances rabbit slow-wave sleep. Am J Physiol, 255 (5 Pt 2), R748-55, 1988.
  65. Shoham, S, Ahokas, RA, Blatteis, CM, Krueger, JM. Effects of muramyl dipeptide on sleep, body temperature and plasma copper after intracerebral ventricular administration. Brain Res, 419 (1-2), 223-8, 1987.
  66. Hunter, WS, Blatteis, CM, Llanos-Q, J, Mashburn, TA, Ahokas, RA. Thermal stimulation of the hypothalamus does not evoke the acute-phase reaction. Brain Res Bull, 19 (1), 69-74, 1987.