PubMed Health⌕ Search

Biomedical subjects

Michael J Parnham

Publications and source records attributed to Michael J Parnham.

8 recordsLinked to original sources
PubMed2006

Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice.

Macrolide antibacterials inhibit the production of various cytokines and the migration of inflammatory cells. These anti-inflammatory actions of macrolides may be beneficial in attenuating inflammatory processes involved in bacterial sepsis. Therefore, we investigated the ability of azithromycin to attenuate the deleterious effects of lipopolysaccharide (LPS), in three different LPS-induced inflammatory models. Our results show that azithromycin (10 and 100 mg/kg) significantly attenuated the intraperitoneal LPS-induced increase in plasma TNF-alpha concentration. It also increased survival rate in a septic shock model in mice challenged with intravenous LPS. Oral treatment with azithromycin (up to 300 mg/kg) was less effective in suppressing neutrophil infiltration into the lungs 24 h after intranasal LPS challenge, possibly because of a slower onset of action or inadequate dosing. In the same model, azithromycin given intraperitoneally significantly improved inflammatory markers (total cell number, neutrophil percentage and MIP-2 concentration) in bronchoalveolar lavage fluid. In conclusion, azithromycin exhibits significant anti-inflammatory properties but the potency of such effects varies depending on the experimental model and route of administration.

Administration, Oral↗
PubMed2005

Modulation of neutrophil and inflammation markers in chronic obstructive pulmonary disease by short-term azithromycin treatment.

The anti-inflammatory potential of azithromycin in chronic obstructive pulmonary disease (COPD) patients was explored following a standard oral dosing regimen. Patients with moderate and severe COPD were treated with azithromycin (500 mg, n=16) or placebo (n=8) once daily for 3 days in a randomized, double blind design, to compare effects on inflammation markers with those seen in a previous study in healthy volunteers. A battery of tests was made on serum, blood neutrophils and sputum on days 1 (baseline), 3, 4, 11, 18 and 32. In comparison to placebo, azithromycin resulted in an early transient increase in serum nitrites plus nitrates (day 3), associated with a tendency towards an increase in the blood neutrophil oxidative burst to phorbol myristic acetate. Subsequently, prolonged decreases in blood leukocyte and platelet counts, serum acute phase protein (including C reactive protein) and soluble E-selectin and blood neutrophil lactoferrin concentrations and a transient decrease in serum interleukin-8 were observed. Blood neutrophil glutathione peroxidase activity showed a prolonged increase after azithromycin treatment. The biphasic facilitatory-then-inhibitory response to azithromycin seen in healthy volunteers is not so clearly detectable in COPD patients, only potential anti-inflammatory effects. Treatment for longer periods may give therapeutic anti-inflammatory benefit in these patients.

Adult↗
PubMed2005

Immunomodulatory effects of antimicrobials in the therapy of respiratory tract infections.

PURPOSE OF REVIEW: Several classes of antibiotics, particularly macrolides and to some extent quinolones, exert modulatory effects on inflammatory cells. With a growing number of experimental and clinical studies being performed, the relevance of the immunomodulatory actions of antibiotics to the therapy of respiratory infections is discussed in the light of recent reports. RECENT FINDINGS: Antibiotics, particularly macrolides, exert both stimulatory and inhibitory effects on leukocytes. These effects seem to be related to the activation state of the leukocytes, facilitating bacterial killing as well as the resolution of local inflammation. In community-acquired pneumonia, this may account for the therapeutic benefit of macrolides, even when bacterial eradication is not complete. A variety of effects of macrolides on Pseudomonas aeruginosa, including the inhibition of biofilm matrix, contribute with immunomodulation to the improvement of respiratory function seen with macrolides in cystic fibrosis. SUMMARY: Macrolides can facilitate the killing of microorganisms in acute respiratory infections through the stimulation of neutrophil activation. On long-term administration, anti-inflammatory, T helper type 1 lymphocyte-enhancing and biofilm-thinning actions, among others, make macrolides valid therapeutic options in chronic infectious/inflammatory disorders, even for infections with microorganisms that are not completely eradicated.

Anti-Bacterial Agents↗
PubMed2005

Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin, telithromycin, and cethromycin.

Macrolide antibiotics have an outstanding ability to concentrate within host cells, particularly phagocytes. In the study described in this paper five different macrolide antibiotics were compared regarding the uptake and release kinetics in human peripheral blood polymorphonuclear neutrophils (PMNs) and three different cell lines, two phagocytic cell lines (RAW 264.7 and THP-1) and an epithelial cell line (MDCK). Based on the results obtained, the substances tested could be clustered into different groups. Azithromycin constituted the first group, characterized by rapid and nonsaturable uptake into phagocytic cells and a high degree of retention in the preloaded cells. The second group included erythromycin and clarithromycin. These two substances do not exhibit cell specificity; consequently, they are taken up to a similar extent and are released by all cell types studied. Ketolides constituted the last group. Their uptake was saturable in cells of monocytic lineage as well as in nondifferentiated cells of myeloid lineage, and they were rapidly released from all the cell lines studied. However, in PMNs, ketolide uptake was not saturable; and unlike telithromycin, cethromycin rapidly egressed from the loaded cells.

Animals↗
PubMed2005

Inflammation 2005 - Seventh World Congress. Respiratory inflammation.

In this conference, unlike previous conferences in this series, relatively little time was given to new drug therapy approaches for the treatment of inflammation. Instead, the emphasis was on basic mechanisms with a strong bias toward Australian research. The etiology of chronic obstructive pulmonary disease (COPD) and asthma was discussed in detail with an intensive consideration of mechanisms involved in the development of corticosteroid resistance, particularly the role of histone deacetylase. Various rodent model systems for testing potential inhibitors of COPD and asthma were also presented.

Adrenal Cortex Hormones↗
PubMed2005

Inflammation 2005 - Seventh World Congress. Rheumatoid arthritis and cell signaling.

Novel targets for antirheumatic therapy were discussed including synoviocyte CD97 and the T-cell co-receptor CTLA-4: an immunoglobulin fusion protein of CTLA-4 (abatacept (Bristol-Myers Squibb Co)) has recently been revealed to be a well-tolerated and effective therapeutic agent for rheumatoid arthritis. Furthermore, cell-signaling molecules were a major topic, and cytoplasmic adaptors of toll-like receptor responses, the kinases JNK and Lyn and the macrophage surface molecule CD200 were considered as potential targets for novel therapies.

Animals↗
PubMed2002

Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects.

Effects on human neutrophils and circulating inflammatory mediators were studied in 12 volunteers who received azithromycin (500 mg/day, p.o.) for 3 days. Blood was taken 1 h before treatment, 2.5, 24 h and 28 days after the last dose. An initial neutrophil degranulating effect of azithromycin was reflected in rapid decreases in azurophilic granule enzyme activities in cells and corresponding increases in serum. The oxidative response to a particulate stimulus was also acutely enhanced. These actions were associated with high plasma and neutrophil drug concentrations. A continuous fall in chemokine and interleukin-6 serum concentrations, within the non-pathological range, accompanied a delayed down-regulation of the oxidative burst and an increase in apoptosis of neutrophils up to 28 days after the last azithromycin dose. Neutrophils isolated from blood at this time point still contained detectable drug concentrations. Acute neutrophil stimulation could facilitate antibacterial effects of azithromycin, while delayed, potentially anti-inflammatory activity may curtail deleterious inflammation.

Acute-Phase Proteins↗