Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Immune function”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed1995

Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor.

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine tumors has been shown to induce immune suppressive cells having homology with GM progenitor cells. The purpose of this study was to determine if human head and neck cancers secrete GM-CSF, if this is associated with an intratumoral presence of similar cells expressing the hematopoietic progenitor cell antigen CD34, and if such CD34(+) cells suppress functions of intratumoral T cells. This was evaluated with fresh head and neck cancers, and in some instances regional lymph nodes and control tissue. Ten of the 14 squamous cell carcinomas (SCCs) studied secreted greater than 5 ng GM-CSF/g tissue. GM-CSF was not secreted in significant levels by either the other cancer types or by control normal muscle. Each of the high GM-CSF-secreting SCCs, but none of the cancers that did not secrete GM-CSF, contained cells expressing the hematopoietic progenitor cell antigen CD34 that had the capacity to grow into colonies in soft agar. Available regional lymph nodes from patients with high GM-CSF-producing cancers also contained CD34(+) cells. Depletion of CD34(+) cells from dissociated cancers increased interleukin 2 secretion by the intratumoral lymphocytes while addition of the CD34(+) cells to dissociated cancers reduced interleukin 2 production, indicating that the presence of CD34(+) cells within GM-CSF-producing head and neck SCCs results in suppressed functional competence of lymphocytes within the SCCs. These results show that GM-CSF-secreting SCCs contain cells expressing the hematopoietic antigen CD34 which are inhibitory to the capacity of lymphocytes within the SCCs to secrete interleukin 2.

Aged↗
PubMed2006

The ICH S8 immunotoxicity guidance. Immune function assessment and toxicological pathology: autonomous or synergistic methods to predict immunotoxicity?

The new ICH S8 guideline on Immunotoxicology Studies for Human Pharmaceuticals indicates that additional, functional testing of pharmaceuticals is not mandatory to screen for unintended immunotoxicity. The usefulness of conventional parameters like clinical pathology, organ weights and histopathology as measured in Standard Toxicity Studies (STS) to screen for potential unintended immunotoxicity was investigated in an ICH survey. Data of this survey appear to support the notion that properly evaluated STS endpoints would be sufficient for the detection of the majority of unintended immunosuppression by investigational pharmaceutical compounds. Thus the ICH S8 guideline was based on a cause for concern approach using a weight of evidence review of various factors like: findings from STS, pharmacological properties of the drug, intended patient population, structural similarities to known immunomodulators, drug disposition and/or clinical information. Overall the S8 guideline allows for more flexible approaches, and requires a weight of evidence review for which there is no given set of rules. For a proper use this asks for a sensible, realistic and above all a responsible approach both from Industry and Regulators. Some examples regarding the use of clinical pathology parameters like immunoglobulin levels and lymphocyte phenotyping have been included to illustrate this. In conclusion, to detect and evaluate potential immunotoxic effects of human pharmaceuticals the ICH S8 guideline allows for a more flexible, scientifically sound approach. For a proper evaluation of potential immunotoxic effects integration of data from standard toxicological parameters like clinical pathology, histopathology and functional assays are important.

Animals↗
PubMed1991

Differential and sex-specific effects of kainic acid and domoic acid lesions in the lateral septal area of rats on immune function and body weight regulation.

The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats.

Animals↗
PubMed1994

Effects of phenytoin administration on murine immune function.

The results obtained in these series of experiments indicate that oral administration of phenytoin (100, 50, or 25 mg/kg) to mice significantly depressed both humoral and cellular immune responses, evaluated by the techniques of enumeration of direct and indirect spleen plaque-forming cells (PFC) and the delayed-type hypersensitivity reaction (DTH) against sheep red blood cells (SR BC), when compared with those observed in normal control animals. Furthermore, spleen cells, purified splenic T lymphocytes or Ly 2 + T cells obtained from 100 mg/kg phenytoin-treated donor mice were capable of diminishing both PFC and DTH responses of normal cells transferred into lethally irradiated mice. The immunodepressor effect of phenytoin was observed despite the fact that administration of this drug induced a rise in spleen cellularity.

Animals↗
PubMed2004

Effect of indinavir used alone or in double or triple combination with AZT and ddC on human immune functions.

Indinavir (IDV) is a potent and selective human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) widely used in antiretroviral therapy, but its effects on the immune system are relatively unknown. In this study we have investigated the in vitro effect of IDV on normal human peripheral blood mononuclear cells (PBMC). We used the drug alone or in double and triple combination with AZT and ddC to assess whether IDV interferes with the previously observed immunomodulatory effects induced by AZT and ddC. We found that proliferative response, induction of immunoglobulins (Ig) production and cytokine production was not modulated by IDV. More importantly, IDV used in double or triple combination with AZT and ddC, does not further strenghten the inhibition of proliferative response induced by AZT and is able to abrogate the inhibitory effect induced by ddC on proliferative response. Similarly, IDV/AZT, IDV/ddC and IDV/AZT/ddC combinations does not strenghten the modulation of TNF-alpha, IFN-gamma and IL-4 induced by AZT, ddC and AZT/ddC. On the other hand, IDV neutralizes the up-regulating effects of AZT on IL-2 production while the up-regulating effects of ddC on IL-2 production is not affected. These data suggest that IDV used in combination with AZT and ddC did not add any further immunotoxicity.

Adjuvants, Immunologic↗
PubMed2006

Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men.

BACKGROUND: Increasing intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) can decrease markers of immunity. However, dose- and age-related responses have not been identified. OBJECTIVE: The objective was to determine the effects of different amounts of eicosapentaenoic acid (EPA) on innate immune outcomes in young and older males. DESIGN: In a controlled, double-blind study, healthy young and older men consumed 1 of 4 supplements provided as capsules: placebo (corn oil) or different amounts of an oil providing 1.35, 2.7, or 4.05 g EPA/d for 12 wk. Blood samples were collected at baseline and after 12 wk. RESULTS: EPA was incorporated in a linear dose-response fashion into plasma and mononuclear cell (MNC) phospholipids; incorporation was greater in the older men. EPA treatment did not alter neutrophil or monocyte phagocytosis, monocyte respiratory burst, or the production of inflammatory cytokines by MNCs in the young or older men. EPA treatment caused a dose-dependent decrease in neutrophil respiratory burst only in the older men. Increased incorporation of EPA into plasma or MNC phospholipids was associated with decreased production of prostaglandin E2 by MNCs from both young and older men. CONCLUSIONS: Older subjects incorporate EPA into plasma and MNC phospholipids more readily than do younger subjects. Other than prostaglandin E2 production, innate immune responses in young subjects are not affected by an EPA intake of < or =4.05 g/d. Older subjects are more sensitive to the immunologic effects of EPA, and the neutrophil respiratory burst is lower at higher EPA intakes.

Adolescent↗