Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance.

We report here a murine model for experimental chronic colitis where administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol induced inflammation of large intestine in susceptible (C3H/HeJ and BALB/c) but not resistant (C57BL/6 and DBA/2) mouse strains. We queried whether mucosal trinitrophenyl (TNP)-specific B cell responses were induced in mice with TNBS-induced colitis, and if induction of tolerance to TNBS by oral administration of this hapten protected mice from development of colitis. Isotypes and subclasses of polyclonal and TNP-specific Ab-forming cells (AFC) were assessed in mucosal and peripheral lymphoid tissues of C3H/HeJ mice with TNBS-induced colitis. Increased numbers of IgA- and IgG-secreting cells were found in the inflamed colon lamina propria. Inflamed colonic tissue also contained high frequencies of IgG anti-TNP AFC (predominantly of IgG1, IgG2a, and IgG2b subclasses); however, anti-TNP responses in noninflamed mucosal tissues of mice with colitis exhibited dominant IgA and IgM with low IgG anti-TNP responses. CD4+ T cells stimulated with TNP-splenocytes produced more IFN-gamma and less IL-4, suggesting a Th1-type response. Oral administration of TNBS before induction of colitis markedly decreased mucosal anti-TNP responses and completely inhibited anti-TNP IgG2a and IgG2b responses. Control mice did not show inhibition of anti-TNP AFC responses or TNBS-induced colitis. Intracolonic sensitization of susceptible C3H/HeJ mice with TNBS induces a localized IgG anti-TNP B cell response in the inflamed tissue, whereas prior oral administration of TNBS results in unresponsiveness to this agent and protects mice from development of TNBS-induced colitis.

Health care in Kazakstan.

Faced with major economic difficulties in the wake of political upheaval, Kazakstan is striving to strengthen its health care system, not only materially but also through the adoption of enlightened approaches by professionals and of beneficial lifestyles by the public at large.

PIP: The fall of the Soviet Empire led to considerable political and economic turmoil in Kazakhstan during its transition to an independent country. Presently, almost all indicators of public health are declining; the health budget fell from 4% of gross national product in 1991 to 1.6% in 1992 and severe pollution, poor nutrition, and increasing consumption of alcohol and cigarettes prevail. Kazakhstan enjoys a high ratio of 400 physicians per 100,000 population, but a shortage of material resources constrains the delivery of quality health care. Civil discord could result unless the interests of different population groups are met. In this context, Kazakhstan is trying to strengthen its health care system. Aid from international, national, and private groups during the past few years has led to improvements in maternal and child health services and in supplies of essential drugs, baby food, vaccines, and medical equipment. Health care facilities in most parts of the country, however, urgently need support and there is a need to develop training programs for administrators, public health professionals, educators, and family planning workers. The control of tuberculosis has received top priority, followed by esophageal cancer.

Differences in intraepithelial lymphocyte T cell subsets isolated from murine small versus large intestine.

Intraepithelial lymphocytes (IELs) have been extensively studied in the murine small intestine. However, to date no studies have assessed IEL in the large intestine, despite the marked differences in function and lumenal environment. In the present study, we isolated IEL from both small and large intestine of three mouse strains (BALB/c, C3H/HeN, C57BL/6) and determined the frequency of CD2, CD4, and CD8 expression on CD3+ IEL, as well as the frequency of alpha beta and gamma delta TCR usage and V beta distribution. Higher numbers of IEL/unit length were always isolated from the small intestine (20-30 x 10(6)/5 mice) compared with large intestine (1.1-2.5 x 10(6)/5 mice). Interestingly, IEL from the large intestine of all strains were predominantly alpha beta TCR+ whereas gamma delta TCR+ IELs predominated in small intestine. Large intestinal IELs were mainly CD4+, in both BALB/c and C3H/HeN mouse strains. IELs from large intestine of C57BL/6 mice were mainly CD8+; however, the CD4+ subset was fourfold higher when compared with small intestine IEL. Potential functional differences between IEL subsets was assessed by determining the relative levels of mRNA for IL-1, 2, 4, 5, 10, IFN-gamma, TGF-beta, and TNF-gamma. Similar patterns of IL-1, IFN-gamma and TNF-alpha were seen while more IL-2, IL-4, IL-5, and IL-10 mRNA was noted in large intestinal IEL. Stimulation of C3H/HeJ IEL with anti-CD3 also resulted in higher levels of IL-3/GM-CSF, IL-4, and IL-6 by IEL from large intestine. These results show that marked differences occur among the T cell subsets present in IELs from mouse small and large intestine.

[The role of precipitating serum antibodies in tuberculosis patients]. / Rol' pretsipitiruiushchikh antitel v syvorotke krovi u bol'nykh tuberkulezom.

The content of serum alpha 1-proteinase inhibitors (alpha 1-PI), alpha 2-macroglobulins, transferrins, albumin, immunoglobulins A, M and G and C3- and C4-complement factors was investigated in a group of patients (n = 35) with pulmonary tuberculosis who showed precipitating antituberculous circulating antibodies having the properties of autoantibodies. A direct relationship between the available circulating antibodies cross-reacting with the tissues and the rate of an extrapulmonary localization of tuberculous process in pulmonary tuberculosis patients, on the one hand, and their inverse relationship to the level of blood alpha 1-PI, on the other, were revealed. It is recommended to define cross-reacting antibodies and alpha 1-PI concentration to predict the risk of extrapulmonary foci of a tuberculous inflammation.

Effect of vitamin E deficiency on oxidative metabolism and antioxidant enzyme activity of macrophages.

In AUG rats, deprived of vitamin E for 90 days, we noted a 3-fold increase of kinetic parameters of luminol-dependent chemiluminescence of macrophages, stimulated with opsonized zymosan, superoxide dismutase activity decrease and increment of plasma membrane lipid bilayer microviscosity, which was estimated by fluorescent probe pyrene eximerization method. Vitamin E deficiency did not affect glutathione peroxidase and glutathione reductase activities of macrophages.

[An increase in activity of natural killer cells in rats with vitamin A deficiency]. / Povyshenie aktivnosti estestvennykh killerov u krys s nedostatochnost'yu vitamina A.

A study was made of the effect of different supply of rats with vitamin A on the membranotoxic activity of natural killers, which was assessed with the use of target cells K-562 labeled with 3H-uridine incubated jointly with splenocytes. The animals were kept on a semi-synthetic diet deprived of vitamin A. This led to a reduction of the body weight and retinol content in the liver. At the same time the membranotoxic activity of splenocytes rose 1.5-fold as compared with controls kept on a balanced diet. Administration of retinol palmitate to the animals with vitamin A deficiency suppressed the activity of natural killers, raising the retinol content in the liver. The intensity of the effects in question depended on the ratio of the effector cells and targets. The possible mechanisms of the potentiation of natural antitumor resistance in animals with vitamin A deficiency are under discussion.

[Possibility of correcting the immune system by using food products]. / Izuchenie vozmozhnosti korrektsii immunoi sistemy s pomoshch'iu pishchevykh produktov.

In experiments on August rats the effect was studied of a product, prepared by freezing and thawing of cabbage followed by inoculation of yeast and lactic acid microorganisms, on the primary immune response to sheep red blood cells and oxidation metabolism in peritoneal macrophages. The product significantly increased the antibody-formation and accumulation of antibody-forming cells in the spleen but did not affect the lumino-dependent chemiluminescence of macrophages stimulated with opsonized zymosan.

[Effect of vitamin E on the oxidative metabolism of macrophages]. / Vliianie vitamina E na okislitel'nyi metabolizm makrofagov.

The oxidative metabolism of macrophages in vitamin E deficiency was studied on Aug-Lac strain rats. Vitamin E deficiency was shown to enhance luminol-dependent chemiluminescence of macrophages stimulated by opsonized zymosan. There was also an increase in microviscosity of macrophage membrane lipid phase, that was estimated with a fluorescent probe. The incubation of macrophages with dl-alpha-tocopherol led to the inhibition of macrophage chemiluminescence. Superoxide dismutase, glutathione peroxidase and glutathione reductase activity was not affected by vitamin E deficiency.

[Effect of pro- and antioxidant food factors on macrophage oxidative metabolism]. / Vliianie alimentarnykh faktorov pro- i antioksidantnogo deistviia na okislitel'nyi metabolizm makrofagov.

The effects of vitamin E deficiency and excess polyunsaturated acids in the diet on luminol-dependent chemiluminescence were studied in Aug-Lac rats. It was chown that experimental prooxidant regiments led to the increase of oxidative metabolism in macrophages stimulated by opsonized zymozan. Vitamin E deficient regimens decreased superoxide dismutase activity of macrophages. In vitro DL-alpha-tocopherol and the synthetic antioxidants BHT and BHA inhibited chemiluminescence of macrophages. Arachidonic acid activated macrophages and induced the formation of oxygen radicals.