PMID- 8784259 OWN - NLM STAT- MEDLINE DCOM- 19961017 LR - 20220408 IS - 0165-5728 (Print) IS - 0165-5728 (Linking) VI - 68 IP - 1-2 DP - 1996 Aug TI - Induction of immunoreactive interleukin-1 beta and tumor necrosis factor-alpha in the brains of rabies virus infected rats. PG - 45-51 AB - Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are important cytokines in the development of brain inflammation during pathological process. During rabies virus infection, the level of these proinflammatory cytokines are enhanced in the brain. In the present study we determined the cellular localization of these two cytokines by immunocytochemistry in brains of rats infected with rabies virus, at different time-intervals of the disease (day 1, 3, 4, 5 and at final stage day 6 post-infection (p.i.)). Cellular identification of IL-1 beta (irIL-1 beta) and TNF alpha (irTNF alpha) immunopositive cells was studied using a polyclonal antibody against these cytokines and against glial fibrillary acidic protein (GFAP) to detect astrocytes and GSA-I-B4 isolectin to detect microglial cells and/or infiltrating macrophages. In brains of control and early infected rats, irIL-1 beta was only detected in fibers located in the hypothalamus, supraoptic and tractus optic nuclei and infundibular nucleus. From day 4 onwards until day 6 p.i., enhanced irIL-1 beta was found and identified either in activated ameboid and/or infiltrated macrophages (amygdala, thalamus, internal capsula, subtantia nigra, septal nuclei and around blood vessels), or in activated ramified cells (hypothalamus and periventricular nucleus, piriformis and cingulate cortex, hippocampus). IrTNF alpha was observed in the brains of rats at a final stage of disease (day 5 and 6 p.i.): in the hypothalamus, the amygdala, the internal capsula, the thalamus, the septal nuclei, the hippocampus, the habenular nuclei and around the blood vessels. Ir-TNF alpha was detected in round cells identified as ameboid microglia and/or infiltrated macrophages. A marked activation of microglial and astroglial cells was observed mainly in the hypothalamus, the thalamus and hippocampus and around the blood vessels, at day 4 p.i. and later, revealing a high central inflammatory reaction in brains of rabies virus infected rats. These results showed that IL-1 beta and TNF alpha are produced in the brain both by local microglial cells and infiltrating macrophages during rabies infection. Thus, these cytokines may play an important role in coordinating the dramatic inflammatory response associated with the rabies-encephalopathy as well as in the neural modification and alteration of brain functions. FAU - Marquette, C AU - Marquette C AD - Rabies Unit, Pasteur Institute, Paris, France. chmarq@pasteur.fr FAU - Van Dam, A M AU - Van Dam AM FAU - Ceccaldi, P E AU - Ceccaldi PE FAU - Weber, P AU - Weber P FAU - Haour, F AU - Haour F FAU - Tsiang, H AU - Tsiang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (Interleukin-1) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Animals, Suckling MH - Brain/*immunology/virology MH - Brain Chemistry/immunology MH - Interleukin-1/*immunology MH - Male MH - Mice MH - Microglia/chemistry/immunology/virology MH - Rabbits MH - Rabies/*immunology MH - Rabies virus/*immunology MH - Rats MH - Rats, Wistar MH - Tumor Necrosis Factor-alpha/*immunology EDAT- 1996/08/01 00:00 MHDA- 2000/06/01 09:00 CRDT- 1996/08/01 00:00 PHST- 1996/08/01 00:00 [pubmed] PHST- 2000/06/01 09:00 [medline] PHST- 1996/08/01 00:00 [entrez] AID - 0165-5728(96)00056-2 [pii] AID - 10.1016/0165-5728(96)00056-2 [doi] PST - ppublish SO - J Neuroimmunol. 1996 Aug;68(1-2):45-51. doi: 10.1016/0165-5728(96)00056-2.