In vitro synthesis of interferon-gamma, interleukin-4, transforming growth factor-beta and interleukin-1 beta by peripheral blood mononuclear cells from tuberculosis patients: relationship with the severity of pulmonary involvement.

Given the role of cell-mediated immune responses in resistance to mycobacteria, we sought to analyse whether there was a relationship between the severity of pulmonary tuberculosis (TB) and lymphocyte proliferation as well as in vitro cytokine production. To achieve this, 25 untreated TB patients showing mild (n = 5), moderate (n = 9) or advanced (n = 11) pulmonary disease, and 12 age-matched healthy controls (mean+/-SD, 37+/-14.5 years) were studied. Peripheral blood mononuclear cells were cultured for 5 days with 10 microg/ml whole, sonicated Mycobacterium tuberculosis (WSA) or 2.5 microg/ml Concanavalin A (Con A). Supernatants were collected on day 4, from cultures grown with or without WSA, for measurement of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-1beta and transforming growth factor-beta (TGF-beta). Antigen-specific proliferation was found to be reduced among patients and more profound in those with advanced disease who also displayed a depressed response to Con A. Patients with mild TB showed a preferential production of IFN-gamma over IL-4, gave the highest level of IFN-gamma synthesis upon specific antigen stimulation and showed increased levels of IL-1beta production. Findings in patients with moderate TB appeared compatible with a mixed production of IFN-gamma and IL-4 coexisting with a higher synthesis of TGF-beta, by comparison to patients with mild TB. Advanced disease showed the highest IL-4 and TGF-beta production, with IFN-gamma synthesis readily noticeable, yet decreased in comparison with the other patient groups. Differences in cytokine response according to the amount of lung involvement suggest a role for such mediators in the immunopathogenesis underlying the distinct clinical forms of pulmonary TB, that is a predominant T helper Th)1-like or Th2-like activity in mild or in progressive TB, respectively.

Impaired in vitro T-cell responses in patients with community acquired pneumonia.

To evaluate the status of the cellular immune response of patients with community acquired pneumonia (CAP), 8 CAP cases were studied for their in vitro T-cell responses to concanavalin A (Con A), tuberculin, and candidin, as well as levels of major T-cell populations in peripheral blood. Assessment on admission revealed that CAP patients had significantly decreased responses to both antigen and mitogen driven lymphocyte proliferation when compared to age and sex matched controls. Studies performed upon 1 week of antibiotic treatment made evident, in turn, that clinical improvement was accompanied by a reestablishment of the in vitro responses to tuberculin and candidin, whereas the lymphoproliferation induced by Con A remained decreased as in its first evaluation. Data from admission and day 7 of treatment showed no significant differences as to the levels of peripheral T-cell subsets when compared to those of healthy controls. Our results indicate that CAP coincides with reduced in vitro T-cell responses to antigen and mitogen stimulation.

Inhalatory anesthetic (halothane) associated changes in the immune response in mice.

The extent of surgery, the patient's age, health status and other factors may contribute to alteration of the immune system during anesthesia and surgery. In addition, inhalatory anesthetics may cause acute and chronic toxicity because of the production of intermediate and end metabolic compounds. The present work was undertaken to evaluate, both in vivo and in vitro, if repeated doses of halothane were able to affect the immune response in a murine model developed at our laboratory. Weekly doses of halothane were administered to mice subjected to no surgery and three days after the last anesthetic-exposure, several immunologic parameters were assessed. Results on the in vivo response to sheep red blood cells showed that halothane treatment increased the amount of specific antibody secreting B-cells, without affecting the delayed type hypersensitivity reaction to the same antigen. In vitro studies on spleen cell composition showed that halothane re-exposure diminished the number of CD4+, CD8+ and B-cells. Such changes were not translated into alterations on the mitogen-driven lymphoproliferation, as well as macrophage phagocytic and lytic functions. Our results indicate that halothane re-exposure is able to modulate the immune response affecting both the number of antibody secreting cells involved in a specific in vivo response, and the splenic lymphoid cell composition. Since such halothane-induced immune alterations might bias the results of a wide range of physiological research, even those involving other systems, a careful selection of the anesthetic agent and methods by which the compound is administered is advisable.

[Concomitant immunity against Sarcoma E 100 comparing 2 strains of rats]. / Inmunidad concomitante contra el Sarcoma E 100 comparando dos líneas de ratas.

Concomitant immunity (IC) is usually defined as the capacity of any animal bearing a progressor tumor to inhibit a second challenge with the same tumor. In order to establish the contribution of the host to the origin of this phenomenon, IC was induced in two lines of rats with a different behavior when challenged with Sarcoma E 100 (SE 100), i.e., line IIMc: 90% take and 100% regression; line "m": 100% take and death. The rats received a second challenge on day 3 (Group II), 7 (III), and 14 (IV), as well as the control groups: II', III' and IV', respectively. The animals reinoculated on day 7 showed a decrease, both in percentage of takes (Fig. 1, III vs III') and tumor surface (Table 1, 2). Likewise, in rats IIMc, a lesser development of the first inoculum (Table 1, Ia vs I') was observed. The Winn assay (Table 3) confirmed the presence of immunocompetent spleen cells (CE) against SE 100 in IIMc rat spleens: namely, 1) immune rats (II), 2) unique tumor bearing rats (IV), 3) first progressor and second negative inoculum (V). In line "m" the percentage of takes was only smaller in the group inoculated conjointly with CE from immune rats (Table 3, VI vs VII). A mere 10% (3/30) of "m" rats were immunized against SE 100. Consequently, these results could attribute the IC, in IIMc rats, to immunological mechanisms, while in "m" it could be due to factor(s) released and/or induced by the first tumor, as proposed by Gorelik.

Inmunidad concomitante contra el Sarcoma E 100 comparando dos líneas de ratas. / [Concomitant immunity against Sarcoma E 100 comparing 2 strains of rats]

Concomitant immunity (IC) is usually defined as the capacity of any animal bearing a progressor tumor to inhibit a second challenge with the same tumor. In order to establish the contribution of the host to the origin of this phenomenon, IC was induced in two lines of rats with a different behavior when challenged with Sarcoma E 100 (SE 100), i.e., line IIMc: 90

take and 100

regression; line [quot ]m[quot ]: 100

take and death. The rats received a second challenge on day 3 (Group II), 7 (III), and 14 (IV), as well as the control groups: II, III and IV, respectively. The animals reinoculated on day 7 showed a decrease, both in percentage of takes (Fig. 1, III vs III) and tumor surface (Table 1, 2). Likewise, in rats IIMc, a lesser development of the first inoculum (Table 1, Ia vs I) was observed. The Winn assay (Table 3) confirmed the presence of immunocompetent spleen cells (CE) against SE 100 in IIMc rat spleens: namely, 1) immune rats (II), 2) unique tumor bearing rats (IV), 3) first progressor and second negative inoculum (V). In line [quot ]m[quot ] the percentage of takes was only smaller in the group inoculated conjointly with CE from immune rats (Table 3, VI vs VII). A mere 10

(3/30) of [quot ]m[quot ] rats were immunized against SE 100. Consequently, these results could attribute the IC, in IIMc rats, to immunological mechanisms, while in [quot ]m[quot ] it could be due to factor(s) released and/or induced by the first tumor, as proposed by Gorelik.

[Effect of intratumor macrophages on the growth of a rat sarcoma]. / Influencia de los macrófagos intratumorales en el crecimiento de un sarcoma de rata.

The removal of active phagocytic cells (CFA) from suspensions of a rat sarcoma (S-E 100) caused a decrease in tumor development in "m" line rats; consequently, we postulated that the macrophage (M phi) population infiltrating the tumor might possess inhibitory functions. In the present paper we investigate whether the effect of CFA is a general one or whether it is dependent on the interaction between M phi infiltrating the tumor and the recipient. S-E 100 was inoculated in "m" line rats (S-E 100,m) and in "c" (S-E 100,c); CFA were depleted from both tumoral suspensions with carbonyl iron powder (FeC), inoculating the supernatant tumor sells denominated S.FeC-m and S.FeC-c, and the corresponding control suspensions, S Te-m and S Te-c. Inocula for both recipients were subcutaneous and contained 1 x 10(6) cells. The elimination of CFA induced a decrease in the development of the tumor in "m" recipients only when the inoculum was provided by S-E 100, m (Table 1). On the contrary no change in tumor growth was detected in the "C" recipients, whether the inoculum was provided by SE-100, m or by S-E 100, c (Table 1). An inhibitory effect on the immune response exerted by M phi infiltrating S-E 100, as a non general effect, is postulated. This effect was obtained only when intratumoral M phi were syngeneic with the recipient and specifically for "m" line.

Influencia de los macrófagos intratumorales en el crecimiento de un sarcoma de rata. / [Effect of intratumor macrophages on the growth of a rat sarcoma]

The removal of active phagocytic cells (CFA) from suspensions of a rat sarcoma (S-E 100) caused a decrease in tumor development in [quot ]m[quot ] line rats; consequently, we postulated that the macrophage (M phi) population infiltrating the tumor might possess inhibitory functions. In the present paper we investigate whether the effect of CFA is a general one or whether it is dependent on the interaction between M phi infiltrating the tumor and the recipient. S-E 100 was inoculated in [quot ]m[quot ] line rats (S-E 100,m) and in [quot ]c[quot ] (S-E 100,c); CFA were depleted from both tumoral suspensions with carbonyl iron powder (FeC), inoculating the supernatant tumor sells denominated S.FeC-m and S.FeC-c, and the corresponding control suspensions, S Te-m and S Te-c. Inocula for both recipients were subcutaneous and contained 1 x 10(6) cells. The elimination of CFA induced a decrease in the development of the tumor in [quot ]m[quot ] recipients only when the inoculum was provided by S-E 100, m (Table 1). On the contrary no change in tumor growth was detected in the [quot ]C[quot ] recipients, whether the inoculum was provided by SE-100, m or by S-E 100, c (Table 1). An inhibitory effect on the immune response exerted by M phi infiltrating S-E 100, as a non general effect, is postulated. This effect was obtained only when intratumoral M phi were syngeneic with the recipient and specifically for [quot ]m[quot ] line.