Effect of Antibiotics on the Immune Response

Hauser, William E.; Remington, Jack S.

doi:10.1016/s0022-5347(17)53529-6

Cited by 27 publications

(32 citation statements)

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“…The action of antimicrobial agents on both humoral and cell-associated immunity is now recognized (2,17). Tetracyclines, cephalosporins, macrolides, and quinolones have been shown to affect human monocyte responses (3,4,20,(29)(30)(31).…”

Section: Resultsmentioning

confidence: 99%

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Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin

Bailly

Pocidalo

Fay

et al. 1991

Antimicrob Agents Chemother

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Antibiotics do not act alone but act in conjunction with the host defense system. In pairticular, it has been shown that some antibiotics can modify cytokine production. We compared the in vitro effiects of three macrolides (roxithroinycin, spiramycin, and erythromycin) actively concentrated by leukocytes on interleukinla, (IL-la), IL-1p, , and tumor necrosis factor alpha. production by human monocytes stimulated with lipopolysaccharide. Our results show that the three macrolides tested have different effects on production of these cytokines. Spiramycin and, to a lesser extent, erythromycin increased total IL-6 production without affecting IL-la, IL-1j0, or tumor necrosis factor alpha production, whereas roxithromycin had no effect. To our knowledge, this is the first time that an antibiotic has been shown to increase IL-6 production.Over the last 20 years, a growing interest in the study of interactions between antimicrobial agents and host defense systems has arisen. In effect, a wide range of antimicrobial agents administered in vivo or in vitro have been reported to modify host immune responses (14,17,31), including cytokine production (3,4,20,29,30).Interleukin-la (IL-la), and IL-1p, IL-6, and tumor necrosis factor alpha (TNF-a) are the major cytokines produced by mononuclear phagocytes (6, 10, 23, 34). They mediate a wide range of biological activities that play a critical role in the induction of inflammatory and immune responses. Although these cytokines are biochemically and immunologically distinct proteins transcribed from different genes, they share a number of activities, such as the induction of fever and acute-phase protein synthesis by the liver (5,12,15,26). They have also been found to exhibit synergy, and each can modulate the production of the others (1,25,33).Macrolides are a class of antibiotics taken up and concentrated by leukocytes; as a result, they can reach intracellular concentrations far higher than those attained in the extracellular medium (8,21,28 Cytokine production. Following adherence, the cells were washed, and 1 ml of fresh serum-free medium was added to the monolayers with 10 p,g of lipopolysaccharide (LPS) (Escherichia coli O.55:B5; Difco) per ml and with or without various concentrations of the antibiotics (1, 10, and 50 ,ug/ml). Cultures were incubated for 18 h at 37°C in a humidified atmosphere of 95% air and 5% CO2. To determine extracellular cytokine concentrations, cell-free supernatants were collected, centrifuged at 800 x g for 10 min, and stored at -70°C until assay. To determine cell-associated cytokine concentrations, the cells remaining in the wells were covered with 1 ml of fresh medium, lysed with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate (CHAPS) (9 mM; Sigma) for 30 min, and stored at -70°C until assay. Addition of CHAPS to any of the recombinant cytokines used in this experiment did not modify the immunoassays.

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Section: Resultsmentioning

confidence: 99%

“…In effect, a wide range of antimicrobial agents administered in vivo or in vitro have been reported to modify host immune responses (14,17,31), including cytokine production (3,4,20,29,30). …”

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confidence: 99%

Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin

Bailly

Pocidalo

Fay

et al. 1991

Antimicrob Agents Chemother

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“…9) Over 30 years ago, some investigators started reporting the effects of antibiotics on the immune response. 10,11) It was reported that macrolides had an immunomodulatory effect 11,12) and attenuated an increase in rat paw volume induced by injecting carregenin into the paws.…”

Section: Discussionmentioning

confidence: 99%

Ciprofloxacin and Pefloxacin Suppress the Inflammatory Response in Rats

Kılıç

Batu

Yıldırım

et al. 2003

JOURNAL OF HEALTH SCIENCE

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“…Figure 4 shows the effects of pretreatment with macrolide antibiotics (EM, CAM, RXM, and AZM) on macrophage cytocidal activity against Candida albi- Antibiotics have biological properties other than direct antimicrobial activity. These include interactions with and alteration in the functions of host phagocytic cells (4,13,15,28). This subject is of importance, since phagocytic cells are essential for controlling almost all infections and are mediators of inflammation.…”

Section: Methodsmentioning

confidence: 99%

Effect of Macrolide Antibiotics on Macrophage Functions

Fujita

Negayama

et al. 1996

Microbiology and Immunology

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Macrolide antibiotics have a variety of actions other than antimicrobial activities. Recently, it has been suggested that macrolide antibiotics act as immunomodulators.In this study, we evaluated the effects of macrolide antibiotics on macrophage functions.For the macrophage, we used the mouse macrophage cell line J774.1. The following effects of macrolide antibiotics on macrophage functions were evaluated: the effect of macrolide antibiotics on macrophage growth; the phagocytosis of beads; cytocidal activity against Candida albicans; and chemotaxis to lipopolysaccharide (LPS). Macrolide antibiotics except for azithromycin significantly stimulated the growth of the macrophage. In addition, pretreatment with macrolide antibiotics except for roxithromycin significantly stimulated the macrophage phagocytosis of beads, macrophage chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans. These results suggest that macrolide antibiotics stimulate macrophage functions. There is increasing evidence that long-term administration of the macrolide antibiotic erythromycin (EM) is effective in the treatment of chronic respiratory infections, probably through actions other than its antimicrobial properties (19). Although the mechanism of the efficacy is uncertain, several hypotheses have been proposed, such as the immunomodulatory action of macrolide antibiotics. Macrolide antibiotics modulate the functions of inflammatory cells such as polymorphonuclear leukocytes, lymphocytes and macrophages (1, 33). In addition, macrolide antibiotics directly affect airway secretory cell (12) and epithelial cell (35) functions. These effects are proposed to explain the efficacy of macrolides in the treatment of inflammatory airway diseases. Several studies have been conducted concerning the interaction between phagocytic cells and macrolide antibiotics. However, there are few reports that evaluate the interaction between macrophage functions and several macrolide antibiotics. With this background, we evaluated various aspects of the interaction between four macrolide antibiotics and macrophages. These studies included the effect on growth, effect on phagocytic activity, effect on chemotaxis to lipopolysaccharide (LPS), and effect of cytotoxicity against Candida albicans. Materials and MethodsMacrophage. We used a murine macrophage cell line, J774.1. This cell line was obtained from the RIKEN Cell Bank (Ibaraki, Japan). This cell line was cultured in RPMI-1640 medium with 10% fetal bovine serum (FBS).Antibiotics. The EM (Japan Dynabot Co., Tokyo), clarithromycin (CAM, Japan Dynabot Co.), roxithromycin (RXM, Roussel Uclaf, Paris, France), and azithromycin (AZM, Pfizer Pharmaceuticals Inc., Japan) were provided by the respective manufacturers. These 4 drugs were dissolved in 90% methanol at a concentration of 2 mg/ml as a stock solution; then diluted with RPMI-1640 medium with 10% FBS. Several final concentrations of macrolide antibiotics (4 concentrations of each antibiotic) were used in the following experimen...

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Effect of Antibiotics on the Immune Response

Cited by 27 publications

References 0 publications

Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin

Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin

Ciprofloxacin and Pefloxacin Suppress the Inflammatory Response in Rats

Effect of Macrolide Antibiotics on Macrophage Functions

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