Potential anti-inflammatory effects of Melaleuca alternifolia essential oil on human peripheral blood leukocytes.

The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and antioxidative effects remain unclear. This study investigated in vitro the possible role of whole Melaleuca alternifolia EO as a modulator of the inflammatory/non-specific immune response by exploring the chemotaxis and kinetic radical oxygen species (ROS) production of leukocytes and cytokine secretion in peripheral blood mononuclear cells (PBMCs) in humans. The influence of Melaleuca alternifolia EO on the chemotaxis under agarose of isolated neutrophils (PMNs) was evaluated. The kinetics of ROS production by stimulated total circulating leukocytes was followed over 2 h by recording the fluorescence intensity of oxidized dihydrorhodamine 123. The effects of this EO on pro-(interleukin IL-2) and anti-(IL-4 and IL10) inflammatory cytokine secretions were determined by ELISA following incubation of PBMCs with the EO for 24 h. Melaleuca alternifolia EO was inefficient on the chemotaxis of PMNs. It exerted an antioxidant effect, reducing ROS production throughout the kinetic study. Melaleuca alternifolia EO inhibited PBMC proliferation, as revealed by a reduction in IL-2 secretion by stimulated lymphocytes. This EO at 0.1% directly increased the secretion of the anti-inflammatory cytokine IL-4 compared with IL-4 secretion without EO (18.5 +/- 10.0 vs 3.3 +/- 1, p < 0.05), and also increased IL-10 secretion at 0.01% (94.9 +/- 38.7 vs 44.1 +/- 18, ns). Melaleuca alternifolia EO may not only act as an anti-inflammatory mediator through its antioxidant activity but may also efficiently protect the organism by reducing the proliferation of inflammatory cells without affecting their capacity to secrete anti-inflammatory cytokines.

Leptin: a proliferative factor for breast cancer? Study on human ductal carcinoma.

Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFalpha and IL-1beta). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic beta cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study.

Anti-inflammatory effects of Melaleuca alternifolia essential oil on human polymorphonuclear neutrophils and monocytes.

OBJECTIVE AND DESIGN: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and anti-oxidative effects remain unclear. In this study, we investigated in vitro the possible role of whole M. alternifolia EO as a modulator of the oxidative response, i.e. reactive oxygen species (ROS) production, of leukocytes (monocytes and polymorphonuclear neutrophils (PMNs)) in humans. METHODS: Whole blood leukocytes from healthy human volunteers (n = 7), isolated from erythrocytes by haemolytic shock, were incubated for 30 min with M. alternifolia EO (0-0.1%) to determine their ROS production by flow cytometry with or without stimulation of cells. We compared the effects of 3 different stimulating agents acting differently on transductional pathways to stimulate the ROS production: a phorbol ester (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) and opsonised zymosan (OZ). RESULTS: As attested by the Krüskall-Wallis test, M. alternifolia EO at 0.1% directly stimulated ROS production by PMNs (x 8.7 vs. 0% EO, p < 0.05) and increased the intracellular ROS produced by monocytes. Whichever the stimulating agent used (PMA, fMLP or OZ), M. alternifolia EO decreased the intracellular ROS production at the dilution of 0.1% by PMNs and monocytes, more so with PMNs. CONCLUSION: M. alternifolia EO may be both a direct active mediator of the bactericidal action of the circulating leukocytes and may be efficient in protecting the organism from an excess of ROS, through an anti-oxidant and radical scavenging activity.