Inhibition of Human Macrophage Inflammation by the b2AR Agonist Salmeterol

Objectives: Human macropahges are an important component of many chronic inflammatory conditions such as Periodontal Disease. Previously we had shown that incubation of murine macrophages with Salmeterol, a long-acting beta-2 Adrenergic receptor agonist, could inhibit the inflammatory response induced by LPS from E. coli. In the present set of experiments, we sought to determine if salmeterol had a similar inhibitory effect on the inflammatory response of the human monocyte/macrophage cell line THP-1.

Methods: We exposed THP-1 cells to the drug salmeterol, then stimulated them to produce an inflammatory reaction with LPS from either E. coli or from Porphyromonas gingivalis (Pg), an oral pathogen implicated in the progression of chronic Periodontitis. Cells and culture supernatants were collected at the appropriate times, and analyzed for the production of TNFa protein by ELISA and TNFa mRNA by qPCR.

Results: We found that pre-incubation of THP-1 cells with salmeterol significantly inhibited their production of the pro-inflammatory cytokine TNFa induced by LPS from either E coli or from Pg. The dose of salmeterol that was found to be effective in inhibiting TNFa production by THP-1 cells stimulated with either E. coli or Pg LPS was effective over range that was similar to the range found to inhibit murine macrophages. Analysis of the mechanism of salmeterol action on THP-1 cells found that TNFa mRNA expression was significantly suppressed when compared to LPS stimulation alone as determined by qPCR analysis.

Conclusions: The results of these experiments demonstrate that salmeterol can significantly inhibit the activation of human macrophages by LPS from either E coli or Pg, and those patients who regularly use of salmeterol may find it to be an effective treatment treating chronic inflammatory conditions such as Periodontal Disease.