Erythromycin exerts in vivo anti‐inflammatory activity downregulating cell adhesion molecule expression

Abstract

1 Macrolides have long been used as anti-bacterial agents; however, there is some evidence that may exert anti-inflammatory activity. Therefore, erythromycin was used to characterize the mechanisms involved in their in vivo anti-inflammatory activity. 2 Erythromycin pretreatment (30 mg kg À1 day À1 for 1 week) reduced the lipopolysaccharide (LPS; intratracheal, 0.4 mg kg À1 )-induced increase in neutrophil count and elastase activity in the bronchoalveolar lavage fluid (BALF) and lung tissue myeloperoxidase activity, but failed to decrease tumor necrosis factor-a and macrophage-inflammatory protein-2 augmented levels in BALF. Erythromycin pretreatment also prevented lung P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA upregulation in response to airway challenge with LPS. 3 Mesentery superfusion with LPS (1 mg ml À1 ) induced a significant increase in leukocyte-endothelial cell interactions at 60 min. Erythromycin pretreatment abolished the increases in these parameters. 4 LPS exposure of the mesentery for 4 h caused a significant increase in leukocyte rolling flux, adhesion and emigration, which were inhibited by erythromycin by 100, 93 and 95%, respectively. 5 Immunohistochemical analysis showed that LPS exposure of the mesentery for 4 h caused a significant enhancement in P-selectin, E-selectin, ICAM-1 and VCAM-1 expression that was downregulated by erythromycin pretreatment. 6 Flow cytometry analysis indicated that erythromycin pretreatment inhibited LPS-induced CD11b augmented expression in rat neutrophils. 7 In conclusion, erythromycin inhibits leukocyte recruitment in the lung and this effect appears mediated through downregulation of CAM expression. Therefore, macrolides may be useful in the control of neutrophilic pulmonary diseases.

Azithromycin and Clarithromycin Inhibit Lipopolysaccharide-Induced Murine Pulmonary Neutrophilia Mainly through Effects on Macrophage-Derived Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-1β

“…That inflammatory mediators produced early after LPS challenge (CXCL1, CXCL2, and TNF-␣) are uninvolved in macrolide-induced decreases in neutrophil accumulation agrees with the findings of Sanz et al (2005). They reported that erythromycin treatment reduced BALF neutrophil counts and lung tissue MPO activity in LPS-challenged rats without effects on CXCL2 (MIP-2) and TNF-␣ levels in BALF.…”

“…Inhibition of adhesion molecule expression by macrolides was reported in a similar animal model (Sanz et al, 2005) and in clinical studies (Parchure et al, 2002;Hillis et al, 2004). However, because these adhesion molecules are induced by both LPS and proinflammatory cytokines, such as TNF-␣ and IL-1␤, the observed inhibition may be indirect, through effects of macrolides on cytokines.…”

“…Because several groups, including ours, have reported that various macrolides inhibit the lipopolysaccharide-induced pulmonary inflammatory response (Kadota et al, 1993;Tamaoki et al, 1995;Sanz et al, 2005;Ivetić Tkalcević et al, 2006;Leiva et al, 2008;Ou et al, 2008), we have used this model to perform an in-depth investigation of the effect of azithromycin and clarithromycin on the inflammatory cascade leading to neutrophil infiltration into lungs after intranasal lipopolysaccharide (LPS) challenge in mice. The effect of macrolides on various cytokines, chemokines, and adhesion molecules induced by LPS challenge was carefully assessed to identify potential biomarkers of their anti-inflammatory activity.…”

Upper Respiratory Tract Infection in Household Contacts of Acne Patients

“…their contacts). Anti-inflammatory effects of tetracyclines have been demonstrated both in vitro and in patients with acne [24,25,26,27,28,29,30,31], Macrolide antibiotics have also been shown to have multiple immunomodulatory effects [32, 33]. An alternative explanation for this interesting finding is that contacts of acne patients who develop URTIs while using antibiotics are less likely to seek care for their own URTIs than contacts of acne patients who develop URTIs while not using antibiotics.…”

Effect of Multiprobiotic «symbiter Acidophilic» Used Against the Background of the Course of Injections of Ceftriaxone Antibiotic on Peritoneal Macrophage Functional Activity in Rat

“…Ймовірною причиною збільшення відносної кількості адгезивних клітин у перитонеальному ексудаті може бути здатність бактеріальних антигенів, що входять до складу препарату «Симбітер ацидофільний», спричиняти міграцію (рекрутинг) макрофагів і/або підвищувати рівень їх адгезивної активності [12]. Застосування цефтріаксону призводило до незначного зменшення числа адгезованих клітин у перитонеальному ексудаті у порівнянні з інтактим контролем, що може бути пояснено імунотоксичною дією антибіотика [5] і/або його негативним впливом на адгезивну активність мононуклеарних фагоцитів [11]. При комбінованому застосуванні цефтріаксону та «Симбітер ацидофільний», кількість адгезованих клітин у перитонеальній порожнині була порівняною із відповідними значеннями у тварин, що отримували цефтріаксон.…”