Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans

Abstract

Doxycycline is an antibiotic used in the treatment of a variety of inflammatory conditions, including periodontitis. Apart from its antimicrobial properties, this drug also has independent antiinflammatory effects at sub-antimicrobial doses. The present study aimed to investigate the effects of low-doses of doxycycline (LDD) on cytokine production by human monocytic cells challenged with the periodontal pathogen Aggregatibacter actinomycetemcomitans, for up to 6h. The simultaneous regulation of 12 cytokines were measured by a Human Cytokine Array Kit. To validate the array findings, selected cytokines were also measured by enzyme-linked immunosorbant assay (ELISA). A. actinomycetemcomitans stimulated the production of tumor necrosis factor (TNF)-, interleukin (IL)-1 , IL-1 , IL-6 and IL-8 by the cells after 6h of challenge, and doxycycline significantly inhibited this effect. The kinetics of this regulation demonstrated an early (within 2h) and significant (P<0.05) inhibition of pro-inflammatory cytokines, with a mild (0.5-fold) up-regulation of the anti-inflammatory cytokine IL-10. The results indicate that LDD acts as an anti-inflammatory agent in human monocytic cells stimulated with A. actinomycetemcomitans. This model provides clear evidence that some of the clinically proven benefits of LDD may be related to its ability to regulate inflammatory mediator release by monocytic cells. This property may contribute to the clinically proven benefits of this antibiotic as an adjunctive treatment for periodontitis.

Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment

“…Atopy-specific taxa included members of the Pasteurellaceae (specifically Aggregatibacter and Haemophilus). Members of Aggregatibacter are associated with periodontal disease driven by high pro-inflammatory cytokines (e.g., TNF-a, IL1B, IL-6 and IL-8;) and reduced levels of IL-10 (51, 52). It is tempting to speculate that airway enrichment of this genus in ANA subjects could contribute to asthma protection through activation of the T1 arm of the immune system.…”

Doxycycline inhibits TREM-1 induction by Porphyromonas gingivalis

“…The biological rationale for its use in periodontal practice is its capacity to modulate host responses, including the inhibition of matrix metalloproteinase (MMP) activity, but also a general anti‐inflammatory effect (Shapira et al ., ; Krakauer & Buckley, ; Gurkan et al ., ; Emingil et al ., ). Indeed, it was recently demonstrated that SDD can inhibit the production of a wide range of pro‐inflammatory cytokines in monocytes challenged with the putative periodontal pathogen Aggregatibacter actinomycetemcomitans (Bostanci et al ., ). Hence, it is suggested that the ample mechanisms of SDD actions can provide significant therapeutic potential for the treatment chronic inflammatory diseases, such as periodontitis, but also systemic diseases such as atherosclerotic cardiovascular disease (Gu et al ., ).…”

“…Release of sTREM‐1 may constitute a marker of systemic inflammation in the course of infections, such as systemic sepsis, septic arthritis, pneumonia (Gibot et al ., , b, c, ; Knapp et al ., ; Collins et al ., ). It has recently been demonstrated that P. gingivalis induces TREM‐1 gene expression in monocytes, which is then released from their cell surface as sTREM‐1 (Liang et al ., ; Bostanci et al ., , b). Moreover, mice inoculated with P. gingivalis exhibited higher TREM‐1 gene expression, compared to their corresponding uninfected controls (Hajishengallis et al ., ).…”

Tetracycline Inhibits Local Inflammation Induced by Cerebral Ischemia via Modulating Autophagy

“…These results were consistent with previous reports. In clinical trials, doxycycline treatment resulted in a profound suppression of IL6 [20] and TNF-α [21]. Jantzie et al found that administration of doxycycline could attenuate the ischemic injury via inhibiting the activation of microglia [22].…”