Immunomodulation by quinones. A model for the use of quinones in the treatment of inflammation.

The therapeutic application of quinones in areas other than oncology, such as in chronic inflammation, has been proposed. However, because of the adverse side-effects on the function and vitality of almost all investigated cell types the therapeutical margin is small. The thiol-conjugating capacity of quinones may, however, be applied to reduce the tissue-damaging effects of stimulated neutrophils. In this paper evidence is provided that particular phenols may be used as precursor molecules of quinones. Secretory products from stimulated neutrophils can convert such phenols into quinones. As under normal conditions stimulated neutrophils are present only in inflamed tissues, quinones will be formed only at these sites.

Acquired resistance to type II collagen-induced arthritis in rhesus monkeys is reflected by a T cell low-responsiveness to the antigen.

Ten out of 14 rhesus monkeys developed arthritis after a single immunization with bovine type II collagen (B-CII). In contrast to primary resistant monkeys, arthritic animals showed a B-CII specific T cell proliferation during the induction phase of the disease. All surviving animals showed a full remission of the disease. Two monkeys acquired resistance to collagen-induced arthritis (CIA) after one period of disease, but in three animals a booster immunization with B-CII induced a slight flare-up. It is demonstrated that B-CII immunized rhesus monkeys have the capacity to restore resistance to CIA. The development of resistance to CIA is reflected by a decreased T cell responsiveness to B-CII. It is shown that the lack of IL-2 plays a role in B-CII-induced T cell low-responsiveness. A potential role of CD8+ T cells in the down regulation of the T cell response to B-CII is discussed.

An ethnopharmacognostic approach to the search for immunomodulators of plant origin.

The search for immunomodulating plant constituents through basic and field inquiries into the literature and practices of traditional Indian medicine is treated. The strategy of data collecting proceeds through aspects of an ethnobotanical, an ethnopharmaceutical, an ethnopharmacological, and an ethnomedical nature. In the experimental immunopharmacognostic phase, immunomodulatory compounds are isolated and purified through action-guided fractionation procedures. The results described here refer to activities found on human complement activation and on PMN leucocytes activation. The immunomodulating plant compounds included in this report were isolated from Azadirachta indica bark, Woodfordia fructicosa flowers, Picrorhiza kurroa roots, and Jatropha multifida latex.

An anti-complementary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera.

The aim of the study is to develop new substances with immunomodulatory activity. To this end, extracts from plants used in traditional medicine are used as starting material. This study deals with the mucilagenous leaf-gel of Aloe vera which is well reputed for its therapeutical effect on inflammatory-based disorders. The purification of an aqueous gel-extract guided by inhibition of complement activity in HPS is described. Using anion-exchange and gel permeation chromatography a highly active polysaccharide fraction was isolated, that is present in the gel in various chain lengths. The polysaccharides consist of several monosaccharides of which mannose is dominant. The inhibition is based on alternative pathway activation, resulting in consumption of C3. With respect to their biological activity the polysaccharides inhibit the opsonization of zymosan in HPS and display adjuvant activity on specific antibody production and the induction of delayed type hypersensitivity in mice.

Effects of low molecular constituents from Aloe vera gel on oxidative metabolism and cytotoxic and bactericidal activities of human neutrophils.

In traditional South-East Asian medicine the therapeutic value of the parenchymous leaf-gel of Aloe vera for inflammatory-based diseases is well-reputed. The aim of this study is to investigate at which level gel-constituents exert their activity. We show here that low -Mr constituents of an aqueous gel-extract inhibit the release of reactive oxygen species (ROS) by PMA-stimulated human PMN. The compounds inhibit the ROS-dependent extracellular effects of PMN such as lysis of red blood cells. The capacity of the PMN to phagocytose and kill micro-organisms at the intracellular level is not affected. The inhibitory activity of the low-Mr compounds is most pronounced in the PMA-induced ROS production, but is significantly antagonized by the Ca-ionophore A23187. It is shown that the inhibitory effect of the low-Mr compounds is the indirect result of the diminished availability of intracellular free Ca-ions.

Activity-guided isolation and identification of Azadirachta indica bark extract constituents which specifically inhibit chemiluminescence production by activated human polymorphonuclear leukocytes.

The A. indica crude aqueous bark extract inhibits the generation of chemiluminescence by activated human polymorphonuclear leukocytes (PMN). Guided by this activity the responsible compounds were purified by extraction with different organic solvents and HPLC. Gallic acid, (+)-gallocatechin, (-)-epicatechin, and (as a 2:1 mixture) (+)-catechin and epigallocatechin were isolated and identified by means of HPLC, TLC, MS, 1H-NMR, UV, and CD data. Commercial samples of gallic acid, (+)-catechin and (-)-epicatechin showed the same effects. To our knowledge the identified catechins have never been described as constituents of A. indica.