Tetracyclines and Host-Defense Mechanisms

Forsgren, Arne; Gnarpe, Håkan

doi:10.1128/aac.3.6.711

Cited by 31 publications

(11 citation statements)

References 15 publications

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“…Previous reports on the effects of tetra cyclines on the phagocytic activity of human PMN have presented evidence for either a depressive effect [2,4,6,7,13,15] or no influence [8,9]. Under certain circum stances a depressive effect was found also in the present system.…”

Section: Discussionsupporting

confidence: 65%

“…Over the years evidence has been produced indicating that this anti biotic may influence the host defence mech anisms [3-7, 13, 15]. Previous reports on the interaction between tetracyclines and the phagocytic system have presented evi dence for a depressive effect [2,4,6,7,13, 15J or no effect [8,9], Besides the report of Adam et al [1] we have not been able to find any investigation indicating that tetracy clines enhance the phagocytic activity of hu man leukocytes. As our primary studies seem to yield similar results, further investi gations were undertaken.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Doxycycline on the Phagocytosis of 32P-Labelled Escherichia coli by Human Polymorphonuclear Cells

Melby¹,

Midtvedt²

1981

Chemotherapy

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A study on the effect of various concentrations (2–100 μg/ml) of doxycycline on the phagocytic activity of human polymorphonuclear cells was undertaken using a radio-labelled strain of Escherichia coli as test particle. In the presence of 10% normal human serum pretreatment with 50–100 μg/ml resulted in a 50% increase in cell-associated radioactivity. When omitting serum during the ingestion phase, or conducting the ingestion phase at 4°C, the ingestive capability was reduced. 2 μg/ml present during the ingestion together with 10% normal human serum reduced the ingestive capability significantly, whereas the presence of 10 μg/ml exerted no significant effect. By the use of ³Η-labelled doxycycline the drug was shown to be firmly fixed to the leukocyte monolayer.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Effects of Doxycycline on the Phagocytosis of 32P-Labelled Escherichia coli by Human Polymorphonuclear Cells

Melby¹,

Midtvedt²

1981

Chemotherapy

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“…In vitro studies of the interaction of antibiotics and the immune system have involved predominantly phagocytic and microbicidal function (6,7,13,19,35). Lehrer (19), for example, found that the sulfonamides interfered with the normal activities of human polymorphonuclear leukocytes, an effect which appeared to be involved with the myeloperoxidase-mediated pathway, and Welch et al (35) showed reduced polymorphonuclear leukocyte activity in the presence of tetracycline and trimethoprim.…”

Section: Discussionmentioning

confidence: 99%

Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans

Domer¹,

Hector²

1987

Antimicrob Agents Chemother

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Immune consequences of gastrointestinal colonization of CD-1 and CBA/J mice with Candida albicans in the presence or absence of continuous antibiotic treatment with penicillin-tetracycline or trimethoprimsulfamethoxazole were investigated. Intubation with C. albicans in the absence of antibiotics resulted in the induction of low but detectable delayed-type hypersensitivity (DTH), demonstrable by footpad testing with a C. albicans wall glycoprotein (GP), and in the stimulation of a moderate level of protective immunity, demonstrable by intravenous (i.v.) challenge. DTH to a membrane extract, BEX, could not be detected in such animals. However, animals colonized in the presence of antibiotics and then inoculated cutaneously prior to being tested for DTH or protective immunity developed significantly enhanced levels of DTH to GP and BEX and were protected to an even greater extent than animals colonized in the absence of antibiotics who were not inoculated cutaneously. The priming effect of colonization, particularly with respect to the antigen GP, was also obvious from an enzyme-linked immunosorbent assay for GP-specific antibody with sera.of mice surviving the i.v. challenge, in that GP-specific antibody was present in the highest titers in colonized animals that had been inoculated cutaneously prior to i.v. challenge. While the antibiotics promoted higher levels of colonization, as evidenced by stomach and fecal cultures of intubated mice, antibiotic administration was not necessary for the induction of C. albicans-specific responses. Moreover, contrary to reports in the literature, antibiotic administration had no adverse effect on the immune responses measured. Females were innately more resistant than males to i.v. challenge with C. albicans, but each sex was capable of developing protective immunity of equal intensity in response to colonization or immunization by cutaneous challenge.

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“…An increase in fluorescence intensity occurred when 4 (4,7,8,12,14). In our study, high concentrations of doxycycline reduced PMNL random migration, CL, and glucose oxidation, whereas minocycline had a marked effect on CL and glucose oxidation.…”

mentioning

confidence: 70%

“…However, in another study, Forsgren and Gnarpe have failed to demonstrate any effect on these functions (7). Oxytetracycline has been reported not to inhibit PMNL functions (7). We have previously shown that doxycycline does not reduce in vivo PMNL migration to skin chambers (10) and have indicated that the impairment of PMNL functions measured in vitro may be due to photo-induced production of toxic oxygen species or due to the divalent cation chelating effect of tetracyclines or both.…”

mentioning

confidence: 99%

Influence of tetracyclines on human polymorphonuclear leukocyte function

Glette¹,

Sandberg²,

Hopen³

et al. 1984

Antimicrob Agents Chemother

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Low concentrations of oxytetracycline, doxycycline, or minocycline (< 10 ,ug/ml) did not influence in vitro polymorphonuclear leukocyte random migration, chemiluminescence, or glucose oxidation. At high concentrations of doxycycline or minocycline (> 10 ,ug/ml), chemiluminescence and glucose oxidation were impaired. High concentrations of doxycycline also reduced random migration. Oxytetracycline did not influence these functions in concentrations up to 100 pug/ml. The inhibiting effect of doxycycline and minocycline was abolished when 4 mM Mg2+ was added to the reaction mixture, and 4 mM Ca2+ partly restored minocycline-inhibited polymorphonuclear leukocyte functions. This indicates that the major effect of tetracyclines on in vitro polymorphonuclear leukocyte functions is mediated by their divalent cation chelating effect and that the results of in vitro experiments are highly dependent on the concentration of divalent cations in the reaction mixtures. The difference between the tetracyclines may be due to differences in lipid solubility, with solubility being highest for minocycline and lowest for oxytetracycline, or to different divalent cation chelating ability.Polymorphonuclear leukocytes (PMNLs) represent cornerstones of host defense against infections (2). The possibility that antimicrobial agents may impair PMNL functions is of particular interest since these drugs are frequently administered to patients with enhanced susceptibility to infection. Several studies have focused on the effect of tetracyclines on PMNL function, but the results of these studies are not consistent. In some studies, (4,8,12,18,24) doxycycline has been shown to reduce PMNL chemotaxis (4, 12), phagocytosis (8, 19), or bactericidal activity (18,24) or all three of these. However, in another study, Forsgren and Gnarpe have failed to demonstrate any effect on these functions (7). Oxytetracycline has been reported not to inhibit PMNL functions (7). We have previously shown that doxycycline does not reduce in vivo PMNL migration to skin chambers (10) and have indicated that the impairment of PMNL functions measured in vitro may be due to photo-induced production of toxic oxygen species or due to the divalent cation chelating effect of tetracyclines or both. The aim of the present study was to examine the influence of oxytetracycline, doxycycline, and minocycline on human PMNL functions in the presence of high and low divalent cation concentrations.MATERIALS AND METHODSLeukocytes. Leukocytes were obtained by dextran sedimentation of heparinized blood (18 U of heparin per ml of blood) from healthy volunteers. After centrifugation of the supernatant (500 x g, 5 min) the red cells were lysed with ammonium chloride solution (0.15 M). The leukocytes used for chemiluminescence (CL) and glucose oxidation assays were washed twice in phosphate-buffered saline. A differential count was made, and the cells were resuspended in Hanks balanced salt solution, containing 20 mg of bovine serum albumin per ml, to make concentrations of 107 PMNLs per ml....

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Tetracyclines and Host-Defense Mechanisms

Cited by 31 publications

References 15 publications

Effects of Doxycycline on the Phagocytosis of <sup>32</sup>P-Labelled <i>Escherichia coli</i> by Human Polymorphonuclear Cells

Effects of Doxycycline on the Phagocytosis of <sup>32</sup>P-Labelled <i>Escherichia coli</i> by Human Polymorphonuclear Cells

Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans

Influence of tetracyclines on human polymorphonuclear leukocyte function

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