Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro production of interleukin-1 (IL-1) by LPS-stimulated adherent peritoneal exudate and spleen cells and alveolar macrophages, and interleukin-2 (IL-2) by concanavalin A-stimulated splenocytes were measured in resistant (C57BL/6J) and susceptible (A/J) inbred mice during the early stages of subacute infections with the African trypanosome, Trypanosoma congolense. Production of IL-1 was severely depressed in both mouse strains as early as 24 hr after intraperitoneal injection of bloodstream trypanosomes. Similarly, in both mouse strains, an early decline in IL-2 activity was observed, followed by partial recovery then depression to subnormal levels. These changes in measurable IL-1 and IL-2 activity in infected mice concurred with progressive depression in the spleen cell proliferative response to the mitogen concanavalin A.
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PMID:Interleukin-1 and interleukin-2 production in resistant and susceptible inbred mice infected with Trypanosoma congolense. 348 76

Depression of the cellular immune responses in mice with disseminated histoplasmosis is associated with deficient production of interleukin-2 (IL-2) by splenocytes. Therefore, we examined whether a highly purified preparation of IL-2, recombinant human IL-2 (rIL-2), could modify the cellular immune responses in infected mice and whether this lymphokine could alter the severity of histoplasmosis in animals. Exogenous rIL-2, at concentrations of up to 1,000 U/ml, failed to augment the proliferative responses to concanavalin A by unfractionated splenocytes or splenic T cells from mice infected for 1 week. In addition, rIL-2 did not modulate the plaque-forming cell response to sheep erythrocytes by splenocytes from these same mice. However, at week 3, rIL-2 in concentrations ranging from 10 to 1,000 U/ml considerably augmented the proliferative response to concanavalin A and plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice. Kinetics studies demonstrated that rIL-2 exerted maximal immunoregulatory activity when added on day 0 or 1 to cultures of splenocytes. In vivo administration of rIL-2, 200 to 20,000 U/day, for 10 days to normal and 3-week-infected mice did not alter the proliferative activity of splenocytes to concanavalin A; 200,000 U of rIL-2 per day actually depressed the proliferative responses of splenocytes from normal and infected mice. In vivo, rIL-2 did not modify delayed-type hypersensitivity responses to sheep erythrocytes or to histoplasmin by normal and infected mice. Moreover, treatment with rIL-2 in vivo did not reduce the number of Histoplasma CFU in spleens of mice. Thus, despite the immunoenhancing effect of rIL-2 in vitro, this lymphokine failed to exert similar effects in vivo.
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PMID:Modulation of cellular immune responses in mice with disseminated histoplasmosis by recombinant interleukin-2. 348 7

The effect of chronic treatment with an immunostimulating agent, bestatin, on age-associated immune decline was assessed in C57BL/6 mice. Animals were given weekly doses of bestatin (100 micrograms/mouse, i.p.) from 7 months of age until death, and immune responses (natural killer cell activity, T cell cytotoxicity in vitro and in vivo, delayed-type hypersensitivity reaction, lymphoproliferative responses to mitogens, production of interleukin-2, macrophage functions) were tested at 11, 15, and 20 months. Most of the functions were reduced in 15-17-month-old mice, but evidence of reduced macrophage activities appeared only in limiting conditions (low lipopolysaccharide stimulation for interleukin-1 production and low concentration of macrophages in the cytostatic test). Bestatin administration produced a transient increase in natural killer (NK) cell activity and in vivo T cell cytotoxicity, followed (15-20 months of age) by a depression of NK and T cell-mediated responses. Only macrophage functions were stimulated in 20-month-old bestatin-treated mice. This unresponsiveness coincides with an accelerated mortality of bestatin-treated mice and a significant increase in the number of spontaneous tumor-bearing animals. The stimulation of T cells by bestatin seems to be mediated by a primary activation of macrophages to release immune mediators. Several reasons for the bestatin-induced immunodepression can be postulated including a high dose of bestatin, leading to toxicity or unresponsiveness; induction of suppressor cells; and overproliferation of T cells due to the mitogenic activity of bestatin, which may act as a promoting factor for tumor development.
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PMID:Acceleration of age-associated immune decline and mortality by early repeated administration of bestatin to C57BL/6 mice. 348 72

A model was developed in C3H mice to investigate the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects. Mice receiving 1200 rad (12 Gy) of head and neck irradiation showed significant depression of delayed-type hypersensitivity, peripheral blood lymphocyte counts, spleen cell counts, and spleen cell production of interleukin-2. Treatment with optimal dosages of thymosin alpha 1 (T alpha-1) produced significant increases in all of these values, in some instances to levels higher than in the nonirradiated controls. In identical experiments with mice irradiated to a portal limited to the pelvic region, T alpha-1 induced only partial remission of the abnormalities. The dose response of T alpha-1 with head and neck irradiation showed a relatively limited dose range for immune restoration, a finding that warrants similar determinations in clinical trials with immunomodulating agents. The results suggest a potential clinical usefulness of T alpha-1 and also interleukin-2 in restoring cellular immunity after irradiation for head and neck cancers. The model appears to be useful for investigating immunomodulating agents before they are clinically evaluated as adjuvants with head and neck irradiation regimens.
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PMID:Suppression of cellular immunity by head and neck irradiation. Precipitating factors and reparative mechanisms in an experimental model. 348 72

Pregnancy is a natural allograft and the mechanisms for its non-rejection are obscure. Depression of maternal cellular immunity was suggested as a possible explanation. Interleukin-2(IL-2) is a lymphokine release from OKT4+ lymphocyte. This factor has a crucial role in the proliferation and differentiation of T cell subsets, and controls functions associated with immune rejection mechanisms. We therefore examined the ability of lymphocytes from women in the 3 trimesters of pregnancy to produce IL-2 in culture. Mononuclear cells were cultured with PHA for 48 h. The IL-2-containing supernatant was added to and supported the proliferation of an IL-2 dependent T cell line. Proliferation of this line indicated the IL-2 content of the added supernatant. Using this assay, IL-2 production in all 3 trimesters of pregnancy was adequate and comparable to that of lymphocytes from non-pregnant women. These results suggest that the proposed defect in cellular immunity during pregnancy is not mediated by an inability of the lymphocytes to produce IL-2.
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PMID:Immunocompetence in pregnancy: production of interleukin-2 by peripheral blood lymphocytes. 350 Jul 80

C57BL/6 (susceptible) and A/J (resistant) mice were infected intravenously with a temperature-sensitive mutant of Salmonella typhimurium. In C57BL/6 mice a marked depression of the proliferative response of spleen cells to B and T mitogens occurred and was maximal at 2-3 weeks post-infection, whereas only minor changes were found in A/J mice. This immunodepression was mediated, at least in part, by adherent cells. Moreover, spleen cells from infected C57BL/6 mice did not produce interleukin-2 (IL-2) after concanavalin A stimulation. The impairment of IL-2 production was not related to a defect in IL-1 release. The addition of IL-2 to spleen cells did not restore their ability to respond to mitogens. The depression of mitogenic responses in infected C57BL/6 mice occurred at a time when increased resistance was present.
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PMID:Impairment of lymphocyte proliferative responses and interleukin-2 production in susceptible (C57BL/6) mice infected with Salmonella typhimurium. 351 42

The capacity of peripheral blood mononuclear cells (PBM) to produce interleukin-2 (IL-2) was studied serially before and following operation in patients undergoing various surgical procedures. In patients who had major surgery, significant decrease in IL-2 activity was observed 1, 3 and 6 days after operation as compared to that before surgery, although there was no significant change throughout the post-operative course in patients undergoing minor surgery. IL-2 activity returned to the pre-operative level by the 8th post-operative day. However, it remained significantly depressed 8 days after surgery in patients who had undergone major surgical procedures of more increasing severity. Distribution of T cell subsets, especially OKT4 positive cells, did not differ significantly from the pre-operative value throughout the post-operative course. However, the depressed production of IL-2 3 days after surgery could be abolished when adherent cells were removed from PBM by plastic adherence procedures. These results indicated that adherent cells, but not quantitative change in T cell subsets, might be responsible for the depression of IL-2 production after surgery.
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PMID:Impaired production of interleukin-2 after surgery. 387 77

The interdependence between immunologic events occurring within acutely rejecting rat cardiac allografts and those in host lymphoid tissues were studied. To evaluate cellular dynamics of allograft infiltration, 111In-labeled thoracic duct lymphocytes from Lewis rats were administered intravenously daily (0 to 7 days after transplantation) to (Lewis X BN)F1 heart-grafted unmodified Lewis rats, sacrificed 24 hours later. Accumulation of thoracic duct lymphocytes in the allografts peaked 4 to 5 days after transplantation. To evaluate whether these changes at the graft site were sufficient to carry on the rejection response in the absence of a sustained host immunologic drive, acutely rejecting (Lewis X BN)F1 cardiac allografts were retransplanted serially at days 1 through 5 into normal syngeneic animals. All these regrafts survived greater than 100 days. Neither infusion of interleukin-2-conditioned medium (100 IU for 7 days intravenously) into regrafted hosts nor preoperative perfusion of the retransplanted hearts with interleukin-2-conditioned medium (300 IU) could complete the rejection process. Using flow cytometry analysis, we then assessed the phenotypic alterations of the mononuclear cells infiltrating the graft. The ratio of T helper: T cytotoxic/suppressor cells, which at day 3 was 1.57, inverted abruptly to 0.67 by days 5 to 6. After retransplantation a dramatic depression in T-lymphocyte subsets occurred, particularly affecting the T cytotoxic/suppressor phenotype. Trafficking studies revealed that the T cells that left the regrafts migrated mainly to spleen and mesenteric lymph nodes and away from bone marrow and peripheral blood of the syngeneic secondary recipients. Finally, histologic manifestations of acute rejection at days 4 to 5 virtually reversed themselves after regrafting. These studies emphasize the systemic nature of the rejection cascade, which depends fully on the host lymphoid system; even late changes in the graft microenvironment are not sufficient to produce final immunologic destruction.
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PMID:Host-graft relationship: the systemic nature of allograft rejection. 389 38

The effects of cyclic nucleotides on the proliferation of cultured T-lymphocytes (CTC) stimulated by either phytohemagglutinin (PHA) or lectin-free interleukin-2 (IL-2) were studied. The addition of either N6,O2-dibutyryl cyclic AMP (DB-cAMP), aminophylline or isoproterenol to CTC cultures significantly suppressed the proliferation of CTC stimulated by either PHA or IL-2. This inhibitory effect was maximal when added at initiation of the assay; however, significant depression was still observed when added 24 h later. When DB-cAMP and aminophylline were added together, the inhibitory effects were additive. When DB-cGMP was added to the CTC cultures, inhibition of both PHA- and IL-2-stimulated cultures was also found, but the degree of activity was considerably less than for DB-cAMP or aminophylline. In contrast, when carbachol was added, no inhibition or modulation in proliferation was seen. Lastly, DB-cGMP was not found to antagonize the inhibitory effect of DB-cAMP, but instead to further increase the level of inhibition. In summary, these studies illustrate that cyclic nucleotides modulate the proliferation of IL-2-stimulated CTC as well as PHA-treated cells. This model system should provide an approach to study, in more depth, the mechanism by which cyclic nucleotides or their inducers can modulate the latter stages of the lymphocyte proliferative response, which is mediated by the lymphokine, IL-2.
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PMID:The effects of cyclic nucleotides on the proliferation of cultured human T-lymphocytes. 609 9

Recent studies have provided evidence that deficient interleukin-2 (IL-2) production by helper T cells contributes to the impaired T-cell-mediated functions observed in aged mice. Since most of these responses depend upon the presence of macrophages, a deficit in the functional capacity or in cell cooperation of macrophages may result in a decrease in immune reactivity. We found in the present study, that in vitro the cytostatic activity of macrophages from aged C57BL/6 (B6) mice is affected only slightly, but that in vivo their number increases with age. The synthesis of IL-1 is reduced when macrophages from aged mice are stimulated in vitro by lipopolysaccharide, but addition of exogenous IL-1 apparently does not restore either the mixed lymphocyte reaction or cytotoxic T lymphocyte generation. Co-cultures of young splenic macrophages with aged T lymphocytes do not restore to normal level the impaired proliferative response to T mitogens of aged B6 mice, but aged splenic macrophages provide a full accessory help for mitogenesis of young T cells. Thus, absorption of IL-1 by phytohemagglutinin-activated T cells is slightly altered in aged mice. IL-2 responsive T cells are not altered since exogenous IL-2 supply in vitro completely reconstitutes cytotoxic T lymphocyte generation after an allogeneic stimulation. Moreover, the number of Lyt 1+ cells is not modified in aged B6 mice. These results suggest that the impaired capacity of macrophages to release IL-1 and of blast T cells to bind IL-1 may contribute to the depression of cell-mediated immune reactivity associated with aging but also that the main defect is a functional lesion of IL-2 production by Lyt 1+ helper T cells.
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PMID:Interleukin-1 synthesis and activity in aged mice. 623 33


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