Systemic inflammatory response associated with augmentation and activation of leukocytes in Candida/indomethacin administered mice.

We have previously shown that the combination of beta-glucan and nonsteroidal anti-inflammatory drugs (NSAIDs) was lethal to mice. In this study, we examined the effect of Candida on this treatment and found that Candida showed similar lethal toxicity when used in combination with indomethacin. It was also confirmed that LPS preparations from various origins and by various procedures did not show lethality. Candida/indomethacin induced lethality was found to be associated with increased number of leukocytes in various organs and activation of these cells. These findings strongly suggest that pathogenic fungi augment the side effects of non-steroidal anti-inflammatory drugs.

[1]  G. Toews,et al.  Pathogenic Yeasts Cryptococcus neoformans and Candida albicans Produce Immunomodulatory Prostaglandins , 2001, Infection and Immunity.

[2]  H. Tamura,et al.  Blood clearance of (1 → 3)‐β‐d‐glucan in MRL lpr/lpr mice , 1996 .

[3]  Y. Adachi,et al.  Immunotoxicity of soluble β-glucans induced by indomethacin treatment , 1998 .

[4]  T. Yadomae 真菌β-1,3-グルカンの構造と生物活性 , 2000 .

[5]  Y. Adachi,et al.  Gradual solubilization of Candida cell wall beta-glucan by oxidative degradation in mice. , 1998, FEMS immunology and medical microbiology.

[6]  S. Yamamura,et al.  Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs. , 1996, Cellular immunology.

[7]  S. Kunkel,et al.  Prostaglandins as endogenous mediators of interleukin 1 production. , 1986, Journal of immunology.

[8]  H. Tamura,et al.  Determination of plasma (1 → 3)-β-d-glucan: A new diagnostic aid to deep mycosis , 1992 .

[9]  S. Shichijo,et al.  Nonsteroidal anti-inflammatory drugs differentially regulate cytokine production in human lymphocytes: up-regulation of TNF, IFN-gamma and IL-2, in contrast to down-regulation of IL-6 production. , 1995, Cytokine.

[10]  X. He,et al.  Prostaglandin E2 selectively inhibits human CD4+ T cells secreting low amounts of both IL-2 and IL-4. , 1999, Journal of immunology.

[11]  F. Paliogianni,et al.  Prostaglandin E2 inhibits the nuclear transcription of the human interleukin 2, but not the Il-4, gene in human T cells by targeting transcription factors AP-1 and NF-AT. , 1996, Cellular immunology.

[12]  R. O. Day,et al.  The Problems and Pitfalls of NSAID Therapy in the Elderly (Part I) , 1991, Drugs & aging.

[13]  N. Sc Non-steroidal anti-inflammatory drugs--uses and complications. , 1992 .

[14]  K. Arai,et al.  Signal transduction in Th clones: target of differential modulation by PGE2 may reside downstream of the PKC-dependent pathway. , 1996, Cytokine.

[15]  C. Shaw-Smith,et al.  Non-steroidal anti-inflammatory drugs: how do they damage the gut? , 1994, British journal of rheumatology.

[16]  S. Abramson,et al.  The mechanisms of action of nonsteroidal antiinflammatory drugs. , 1989, Arthritis and rheumatism.

[17]  M. Betz,et al.  Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. , 1991, Journal of immunology.

[18]  U. Grohmann,et al.  Evidence for tumor necrosis factor alpha as a mediator of the toxicity of a cyclooxygenase inhibitor in Gram-negative sepsis. , 1996, European journal of pharmacology.

[19]  F. Mustafa,et al.  Candida albicans and Saccharomyces cerevisiae cell wall mannans produce fever in rats: role of nitric oxide and cytokines. , 2000, Life sciences.

[20]  Y. Adachi,et al.  Association of immunological disorders in lethal side effect of NSAIDs on beta-glucan-administered mice. , 2001, FEMS immunology and medical microbiology.

[21]  V. Wright Historical overview of non-steroidal anti-inflammatory drugs. , 1995, British journal of rheumatology.

[22]  Y. Adachi,et al.  Solubilization of yeast cell-wall beta-(1-->3)-D-glucan by sodium hypochlorite oxidation and dimethyl sulfoxide extraction. , 1999, Carbohydrate research.

[23]  E. Akarsu,et al.  Polysaccharide mannan components of Candida albicans and Saccharomyces cerevisiae cell wall produce fever by intracerebroventricular injection in rats , 1999, Brain Research Bulletin.

[24]  Y. Adachi,et al.  Characterization of sodium hypochlorite degradation of beta-glucan in relation to its metabolism in vivo. , 1996, Chemical & pharmaceutical bulletin.

[25]  H. Tamura,et al.  Activation of limulus coagulation factor G by several (1-->3)-beta-D-glucans: comparison of the potency of glucans with identical degree of polymerization but different conformations. , 1993, Journal of biochemistry.

[26]  S. Kohno,et al.  Plasma (1→3)-β-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes , 1995, The Lancet.

[27]  J. Vane,et al.  Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. , 1971, Nature: New biology.

[28]  T. Sugiura,et al.  Sensitivity Difference to the Suppressive Effect of Prostaglandin E2 Among Mouse Strains: A Possible Mechanism to Polarize Th2 Type Response in BALB/c Mice , 2000, The Journal of Immunology.