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Hypothalamic and other central influences on antibiosis and host immunity
WS19-3
*3
CORRELATION BETWEEN THE PRIMING EFFECT OF MURAMYL PEPTIDES FOR INDUCTION OF TNF PRODUCTION AND THEIR PROTECTIVE EFFECT AGAINST BACTERIAL INFECTIONS. M. Parant Institut Biom#dical des Cordeliers, 75270 Paris, France Muramyl dipeptide (MDP) and certain hydrophilic and lipophilic derivatives enhance the nonspecific resistance of mice to bacterial infections. A possible role of tumor necrosis factor (TNF) was investigated because of the protective effect of human and mouse rTNF in infected mice, and of the capacity of the synthetic compounds to stimulate the production of TNF in vitro b), monocytes/macrophages. In vivo, MDPs alone did not induce the release of detectable levels of TNF in the blood whereas 2 hours after LPS administration, the TNF titer was about 400 U/ml, as estimated b)' the cytotoxic effect on actinomycin D-treated L929 cells. A strong increase in TNF yield was obtained when mice had received an MDP injection before LPS, and a kinetic study showed that the peak of the response was attained when the time interval before the challenge was 6 hours. A similar elevation in TNF titer was produced in animals challenged with killed bacteria instead of LPS. The TNF activity in mouse sera was inhibited by antibodies raised to rMuTNF. Among twelve MDP derivatives used in this stud)-, it was observed that only those able to protect against an infectious challenge were capable of potentiating the effect of LPS on 7NF production.
W S 1 9 - 4 *4 IMMNOMODULATING EFFECTS OF OXALYSIN~ X. Y. Li, L. M. Tong, Y. F. Jin, C. Y. Cao, J. F. Wang and P. P. Zhu Shanghai Inst. Materia Medica, Chinese Academy of Sciences, Shanghai, China L-4-Oxalysine is an antibiotic metabolite isolated from a new species of Streptomyces roseoviridofuscus n. sp. in north China.
It inhibited the
growth of several animal transplanted tumors and protected liver injuries from acute and chronic CC14 intoxications.
Clinical trials showed improve-
ment of both liver function and blood flow in patients suffered with chronic viral hepatitis.
Oxalysine 100 mg/kg ip or po administration
to C57/BL mice
for 5 days caused a marked increase in spleen PFC, serum hemolysin, C3 levels.
transformation and elevated the DTH response to SP~BC. considered
IgG and
0xalysine 50-100 mg/kg ip for 3 days promoted spleen lymphocyte It is therefore
that the immunopotentiating effects of oxalysine is benefit to
the immunodeficient
state in cancer and chronic viral hepatitis.
W S 1 9 - 5 -5 HYPOTHALAMIC AND OTHER CENTRAL INFLUENCES ON ANTIBIOSIS AND ~OST I~MUNITY A. Szentivanyi, K. Haberman, O. Heim, P. Schultze, G. Filipp, and S. Reiner, Departments of Pharmacology and Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, U.S.A. and University of Saarland, Saarbrucken, F.R.G. Using permanently implanted depth-electrodes placed stereotaxically in hypothalamic and other brain regions, various nuclear groupings were electrolytically eliminated or conversely, stimulated in guinea pigs and rats that were given graded numbers of killed bacteria pre-treated with subinhibitory concentrations of antibiotics. On the tenth post-operative day, the animals were administered the pre-treated organisms, and 4 days later parameters of bacterial immunogenecity were tested. The latter included production of agglutinins, blastogenic response, passive cutaneous anaphylaxis, delayed type hypersensitivity, lymphocytic cAMP, cGMP, and ~-adrenoceptor densities. In general, lesions in the anterior and ventromedial hypothalamus caused a significant reduction in the antibiotic-enhanced immunogenecity together with increased lymphocytic c ~ and 6adrenoceptor densities, and decreased cGMP concentrations. Lesions in the posterior hypothalamus, mamillary bodies, demonstrated a reverse pattern of responses, whereas those of the hippocampus, amygdaloid comple>: showed a less consistent pattern, and no change in the case of those of the fornix and frontal cortex. Significance of these findings with respect to immunoregulation in general, and antibiosis and host immunity in particular, will be discussed.
150
*3
CORRELATION BETWEEN THE PRIMING EFFECT OF MURAMYL PEPTIDES FOR INDUCTION OF TNF PRODUCTION AND THEIR PROTECTIVE EFFECT AGAINST BACTERIAL INFECTIONS. M. Parant Institut Biom#dical des Cordeliers, 75270 Paris, France Muramyl dipeptide (MDP) and certain hydrophilic and lipophilic derivatives enhance the nonspecific resistance of mice to bacterial infections. A possible role of tumor necrosis factor (TNF) was investigated because of the protective effect of human and mouse rTNF in infected mice, and of the capacity of the synthetic compounds to stimulate the production of TNF in vitro b), monocytes/macrophages. In vivo, MDPs alone did not induce the release of detectable levels of TNF in the blood whereas 2 hours after LPS administration, the TNF titer was about 400 U/ml, as estimated b)' the cytotoxic effect on actinomycin D-treated L929 cells. A strong increase in TNF yield was obtained when mice had received an MDP injection before LPS, and a kinetic study showed that the peak of the response was attained when the time interval before the challenge was 6 hours. A similar elevation in TNF titer was produced in animals challenged with killed bacteria instead of LPS. The TNF activity in mouse sera was inhibited by antibodies raised to rMuTNF. Among twelve MDP derivatives used in this stud)-, it was observed that only those able to protect against an infectious challenge were capable of potentiating the effect of LPS on 7NF production.
W S 1 9 - 4 *4 IMMNOMODULATING EFFECTS OF OXALYSIN~ X. Y. Li, L. M. Tong, Y. F. Jin, C. Y. Cao, J. F. Wang and P. P. Zhu Shanghai Inst. Materia Medica, Chinese Academy of Sciences, Shanghai, China L-4-Oxalysine is an antibiotic metabolite isolated from a new species of Streptomyces roseoviridofuscus n. sp. in north China.
It inhibited the
growth of several animal transplanted tumors and protected liver injuries from acute and chronic CC14 intoxications.
Clinical trials showed improve-
ment of both liver function and blood flow in patients suffered with chronic viral hepatitis.
Oxalysine 100 mg/kg ip or po administration
to C57/BL mice
for 5 days caused a marked increase in spleen PFC, serum hemolysin, C3 levels.
transformation and elevated the DTH response to SP~BC. considered
IgG and
0xalysine 50-100 mg/kg ip for 3 days promoted spleen lymphocyte It is therefore
that the immunopotentiating effects of oxalysine is benefit to
the immunodeficient
state in cancer and chronic viral hepatitis.
W S 1 9 - 5 -5 HYPOTHALAMIC AND OTHER CENTRAL INFLUENCES ON ANTIBIOSIS AND ~OST I~MUNITY A. Szentivanyi, K. Haberman, O. Heim, P. Schultze, G. Filipp, and S. Reiner, Departments of Pharmacology and Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, U.S.A. and University of Saarland, Saarbrucken, F.R.G. Using permanently implanted depth-electrodes placed stereotaxically in hypothalamic and other brain regions, various nuclear groupings were electrolytically eliminated or conversely, stimulated in guinea pigs and rats that were given graded numbers of killed bacteria pre-treated with subinhibitory concentrations of antibiotics. On the tenth post-operative day, the animals were administered the pre-treated organisms, and 4 days later parameters of bacterial immunogenecity were tested. The latter included production of agglutinins, blastogenic response, passive cutaneous anaphylaxis, delayed type hypersensitivity, lymphocytic cAMP, cGMP, and ~-adrenoceptor densities. In general, lesions in the anterior and ventromedial hypothalamus caused a significant reduction in the antibiotic-enhanced immunogenecity together with increased lymphocytic c ~ and 6adrenoceptor densities, and decreased cGMP concentrations. Lesions in the posterior hypothalamus, mamillary bodies, demonstrated a reverse pattern of responses, whereas those of the hippocampus, amygdaloid comple>: showed a less consistent pattern, and no change in the case of those of the fornix and frontal cortex. Significance of these findings with respect to immunoregulation in general, and antibiosis and host immunity in particular, will be discussed.
150