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PubMed2004

Modulation of host immunity by HIV may be partly achieved through usurping host autonomic functions.

Modulation of host immunity has been observed in human immunodeficiency virus (HIV) infections. HIV is believed to influence host immunity through a variety of mechanisms including direct effects on host T cell survival, indirect effects on cytokine profile through modulation of immune cells, and modulation of endocrine functions that affect immunity such as steroids. We hypothesize that HIV infection may also alter host immunity through modulation of host sympatho-vagal balance. Specifically, we propose that HIV drives autonomic balance towards sympathetic bias, which can contribute to a T helper (Th)2 type immunity. A variety of paraviral syndromes associated with HIV infection such as QT prolongation, cachexia, cardiomyopathy, and lipodystrophy are consistent with evidence of autonomic dysfunction. Immunomodulatory effects of autonomic dysfunction toward Th2 bias are presented. A plausible mechanism by which HIV can influence autonomic balance through hypothalamic manipulation is offered. Shift to Th2 dominance is associated with HIV disease progression and can be viewed as a viral adaptation to promote its own survival. Autonomic remodeling by HIV may exemplify this phenomenon. Our hypothesis has implications for treatment of HIV and its associated syndromes.

Autonomic Nervous System Diseases↗
PubMed2002

Study of autoimmunity in Klinefelter's syndrome and idiopathic hypogonadotropic hypogonadism.

Sex hormones play an important role in determining the progression and severity of autoimmune diseases, but the in vivo mechanisms underlying this relation are poorly understood. The main objective of current study has been to compare the changes in neuroendocrine immune features and autoantibody profile in male patients with hypogonadotropic and hypergonadotropic hypogonadism, and to determine the relationships between sex hormones and immunologic parameters. Thirty-seven male patients with Klinefelter's syndrome and 35 men with idiopathic hypogonadotropic hypogonadism who had no history of previous hormonal therapy and 30 healthy men were recruited in the study. Serum autoantibody profile, sex hormones, and immunologic parameters were studied. In conclusion, our findings suggest that both humoral and cellular immunity is enhanced in male hypogonadism. Klinefelter's syndrome patients also had increased frequency of antiextractable nuclear antibodies and anticardiolipin antibodies positivity compared to idiopathic hypogonadotropic hypogonadism patients. It is possible that testosterone deficiency and increased levels of estradiol are primary responsible factors for this enhanced autoantibody production in Klinefelter's syndrome patients.

Adult↗
PubMed2005

Gene expression profiles differ markedly in mouse strains that are (or are not) susceptible to hyperthyroidism induced using thyrotropin receptor-expressing adenovirus.

BALB/c mice are susceptible and C57BL/6 mice are resistant to Graves' hyperthyroidism induced by immunization with adenovirus encoding the thyrotropin receptor (TSHR) A-subunit. Both strains develop comparable levels of TSHR antibodies, but potent TSH blocking antibody activity in C57BL/6 mice likely blocks development of hyperthyroidism. We used microarrays to compare gene expression in spleens of mice immunized with A-subunit adenovirus (TSHR-Ad) or control adenovirus (Con-Ad). To preclude the effects of variable thyroxine (T(4)) levels, mice were studied when euthyroid as follows: BALB/c mice immunized three times with TSHR-Ad or Con-Ad and C57BL/6 mice immunized three times with TSHR-Ad or Con-Ad. Among the 14,000 expressed probe sets, there were no statistically significant differences in gene expression in BALB/c mice immunized with TSHR-Ad versus Con-Ad. In contrast, expression of 57 transcripts (representing 40 genes) changed in response to TSHR-Ad in C57BL/6 mice. Diverse genes were identified, including proteins involved in immune responses, inflammation, and cell cycling as well as heat-shock proteins and proteases. Down-regulation of chitinase 3- and-4 gene expression likely reflects cytokines produced by T-helper 2 (Th2) type cells. Indeed, the immunoglobulin (IgG) subclass for TSHR antibodies reflects a deviation away from Th2 cytokines and toward Th1 in C57BL/6 mice. In conclusion, TSHR-Ad immunization altered gene expression profiles in C57BL/6, but not in BALB/c, mice. This response primarily involved reduced gene expression. In C57BL/6 mice, decreased expression of genes such as cathelicidin, calgranulins, and lipocalin following TSHR A-subunit adenovirus immunization suggests the importance of innate immunity in this response.

Adenoviridae↗
PubMed2001

Gene expression physiology and pathophysiology of the immune system.

Genomic-scale gene expression profiling can reveal cellular physiology with unprecedented richness. This technology is being used to define the gene expression targets of individual regulatory proteins and signaling pathways. Comprehensive databases of gene expression measurements can be used to understand the pathological mechanisms underlying disease processes.

Animals↗
PubMed2024

Identification of key immune-related genes and potential therapeutic drugs in diabetic nephropathy based on machine learning algorithms.

BACKGROUND: Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN. METHODS: We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB. LASSO regression, SVM-RFE, and random forest analysis identified four hub genes (EGF, PLTP, RGS2, PTGDS) as proficient predictors of DN. The model achieved an AUC of 0.995 and was validated on GSE142025. Single-cell RNA data (GSE183276) revealed increased hub gene expression in epithelial cells. CIBERSORT analysis showed differences in immune cell proportions between DN patients and controls, with the hub genes correlating positively with neutrophil infiltration. Molecular docking identified potential drugs: cysteamine, eltrombopag, and DMSO. And qPCR and western blot assays were used to confirm the expressions of the four hub genes. RESULTS: Analysis found 95 and 88 distinctively expressed immune genes in the two DN datasets, with 14 consistently differentially expressed immune-related genes. After machine learning algorithms, EGF, PLTP, RGS2, PTGDS were identified as the immune-related hub genes associated with DN. In addition, the mRNA and protein levels of them were obviously elevated in HK-2 cells treated with glucose for 24 h, as well as their mRNA expressions in kidney tissues of mice with DN. CONCLUSION: This study identified 4 hub immune-related genes (EGF, PLTP, RGS2, PTGDS), as well as their expression profiles and the correlation with immune cell infiltration in DN.

Diabetic Nephropathies↗
PubMed2003

New therapeutic strategies in allergic diseases.

During the past 10 years, strong evidence has been provided to suggest that type 2 T herpes (Th2) responses to 'innocuous' environmental antigens (allergens) play a critical triggering role in the development of allergic disorders. The important role of Th2 cytokines, IL-4, IL-5, IL-9, IL-13, in accounting for most pathophysiological manifestations of atopic allergy has been largely clarified by a series of studies performed in both human diseases and experimental animal models of allergy and asthma. Moreover, the mechanisms responsible for Th2-polarized responses against allergens in atopic subjects, as well as the nature of transcription factors involved in the Th2 polarization, have been identified. Likewise, the role of chemoattractants and chemoattractant receptors, as well as of adhesion molecules, in favoring and amplifying the allergic inflammation has been established. The new insights into the pathophysiology of T cell responses in atopic diseases are providing exciting opportunities for the development of novel immunotherapeutic strategies. These include either nonallergen-specific or allergen-specific regimens. In patients with severe atopic disorders, the possibility of nonallergen-specific strategies designed to target Th2 cells; molecules involved in Th2 differentiation, such as Th2-selective transcription factors, or Th2-dependent effector molecules, such as Th2 cytokines, IL-4, IL-5, IL-9, and IL-13; Th2-related chemokines and/or receptors, or IgE antibody, are being considered. In the majority of atopic subjects affected by mild or moderate allergic diseases, allergen-specific immunotherapies probably would be better. To that end, there are presently two main lines of research, one based on the induction of immune suppression and the other on the redirection of allergen-specific Th2 cell responses to a less polarized profile of cytokine production (immune deviation).

Humans↗
PubMed2006

Development of a guinea pig immune response-related microarray and its use to define the host response following Mycobacterium bovis BCG vaccination.

Immune responses in the guinea pig model are understudied because of a lack of commercial reagents. We have developed a custom-made guinea pig oligonucleotide microarray (81 spots) and have examined the gene expression profile of splenocytes restimulated in vitro from Mycobacterium bovis BCG-vaccinated and naive animals. Eleven genes were significantly (P < 0.05) up-regulated following vaccination, indicating a Th1-type response. These results show that microarrays can be used to more fully define immune profiles of guinea pigs.

Animals↗
PubMed1983

Cytomegalovirus-infected cell polypeptides immune-precipitated by sera from children with congenital and perinatal infections.

Congenital or perinatally acquired human cytomegalovirus (CMV) infections in children may be symptomatic or asymptomatic. In this study, we characterized the electrophoretic properties of CMV-infected cell polypeptides immune-precipitated by sera from children with different types of CMV infections from birth to 4 years of age. Sodium dodecyl sulfate-polyacrylamide gel analysis of immune precipitates formed with radiolabeled extracts of cells infected with CMV strain AD169 showed the following. (i) Electrophoretic profiles of CMV polypeptides immune-precipitated by sera from children with perinatal and congenital infections were similar. At least 11 polypeptides with apparent molecular weights of 150,000, 140,000, 110,000, 100,000, 74,000, 66,000, 50,000, 49,000, 34,000, 25,000, and 20,000 were precipitated. Antibody titer in anticomplement immunofluorescence tests and virus titer in urine correlated with the intensity of polypeptide profiles in autoradiograms. (ii) The initial immune response of children with symptomatic congenital infections was delayed as compared to that of children with asymptomatic congenital and perinatal CMV infections. Sera obtained serially from symptomatic children for years after birth continued to precipitate CMV polypeptides, whereas sera from children with subclinical congenital infections precipitated lesser amounts over time. (iii) Immune precipitates obtained with sera from CMV-infected patients and with monoclonal antibodies to CMV contained polypeptides with comparable electrophoretic and immunological properties.

Antibodies, Monoclonal↗
PubMed2002

Serodiagnostic and immunoprophylactic potential of a 78kDa protein of Leishmania donovani of Indian origin.

BACKGROUND: The serodiagnosis of visceral leishmaniasis due to Leishmania donovani using crude parasite antigen is complicated in many endemic areas by cross-reactions with serum from humans infected with other protozoan diseases. The search for pure antigens avoiding such cross-reactions is in progress. Developing a vaccine against cutaneous leishmaniasis has been much more successful than against visceral leishmaniasis. Immunoprophylactic studies using various combinations of antigens and adjuvants are also in progress, and several strategies are in use, with varying degrees of success. MATERIAL/METHODS: Promastigotes of Leishmania donovani were used. The 78kDa protein was purified by a monoclonal antibody tagged CNBr sepharose CL-4B column. The presence of the protein in both stages of the parasite and in kala-azar patient serum was analyzed by western blotting. ELISA was used for serodiagnosis and isotype analysis of antibodies produced in immunized mice. Immunoprophylactic studies were carried out based on in vitro transformation of amastigotes to promastigotes. RESULTS: The 78 kDa membrane protein, present in both amastigote and promastigote forms of the parasite, was purified to homogeneity. The protein was found to have serodiagnostic potential to detect kala-azar. BALB/c mice immunized with 78kDa protein revealed reduction in spleen parasitemia. Isotype profiles of antibodies produced by immunized mice showed increased production of IgG2a and decreased IgG1 levels. CONCLUSIONS: Our results demonstrated, for the first time, the serodiagnostic and immunoprophylactic use of a pure membrane protein isolated from Leishmania donovani of Indian origin.

Animals↗
PubMed2003

Streptococcus iniae: serological differences, presence of capsule and resistance to immune serum killing.

The biochemical profiles, presence of capsule, outer membrane protein profiles and serological interactions of isolates of Streptococcus iniae obtained from different geographical and fish host origins were examined. The isolates had very similar biochemical profiles using API 20 Strep but varied as to whether they were arginine dihydrolase-negative, -positive or -intermediate (AD-ve, AD+ve, AD+/-ve, respectively). Representatives of each AD type were compared in subsequent experiments. All types possessed a polysaccharide capsule. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of outer membrane proteins or whole cells revealed no difference in banding patterns between isolates. All isolates were resistant to trout normal and specific immune serum and grew well in the presence of added fresh normal serum. Serological analyses of the isolates revealed antigenic differences. Trout antiserum against the AD+ve isolate did not agglutinate the AD-ve or AD+/-ve isolates, while antisera against the latter 2 types showed low agglutinating activity with all 3 isolates. When whole live cells of AD-ve and AD+ve isolates were dot-blotted, antiserum to the AD+ve isolate did not stain the AD-ve isolate, but antiserum to the AD-ve isolate stained both AD types. However, if the cells were pre-treated with Proteinase K (to remove surface-exposed protein antigens), the AD+ve isolate was stained only by its homologous antiserum. These results suggest that while certain protein antigens of the different AD type strains are immunologically cross-reactive, the capsular antigens appear to be AD type-specific. Furthermore, the results suggest that the cross-reactive antigens on the AD-ve isolate are effectively hidden by the strain-specific capsule, while they are partially exposed on the AD+ve isolate.

Agglutination Tests↗
PubMed2006

Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process?

Ovulation is a complex process initiated by the preovulatory LH surge, characterized by cumulus oocyte complex (COC) expansion and completed by the release of a mature oocyte. Although many ovarian genes that impact ovulation have been identified, we hypothesized that genes selectively expressed in COCs would be overlooked by approaches using whole ovary or granulosa cell samples. RNA isolated from COCs collected from preovulatory follicles of equine chorionic gonadotropin (CG) primed mice and at selected times after human CG treatment was subjected to microarray analyses and results confirmed by RT-PCR analyses, Western blotting, and immunofluorescent studies. A remarkable number of genes were up-regulated in COCs including Areg, Ereg, and Btc. Several genes selectively expressed in cumulus cells compared with granulosa cells were related to neuronal (Mbp, Tnc, Nts) or immune (Alcam, Pdcd1, Cd34, Cd52, and Cxcr4) cell function. In addition to Sfrp2, other members of the Wnt/Fzd family (Sfrp4, Fdz1 and Fdz2) were expressed in COCs. Thus, there is a cumulus cell-specific, terminal differentiation process. Furthermore, immunofluorescent analyses documented that cumulus cells are highly mitotic for 4-8 h after human CG and then cease dividing in association with reduced levels of Ccnd2 mRNA. Other down-regulated genes included: Cyp19a1, Fshr, Inhb, and the oocyte factors Zp1-3 and Gja4. In summary, the vast number of matrix, neuronal, and especially immune cell-related genes identified by the gene- profiling data of COCs constitutes strong and novel evidence that cumulus cells possess a repertoire of immune functions that could be far greater than simply mediating an inflammatory-like response.

Animals↗
PubMed1985

Pregnancy outcome in human couples with recurrent spontaneous abortions: HLA antigen profiles; HLA antigen sharing; female serum MLR blocking factors; and paternal leukocyte immunization.

Critical features of the trophoblast for immune protection in the mother are: (1) its resistance to cytotoxic lymphocytes and antibodies; (2) it forms a physical barrier to immune effector cells, but not antibody, from reaching the fetus; (3) it signals the migration of suppressor and other functionally hyporesponsive lymphocytes into the uterine decidua and uterine lymphatics; (4) it promotes the production of maternal serum MLR (mixed lymphocyte reaction) blocking antibody with paternal antigen specificity. Some of these immunological features are lacking in women with recurrent abortions of immune etiology. Eleven women who aborted an additional time after immunization with paternal leukocytes were compared with 14 women who delivered infants at term post-immunization. It was found that those who aborted: (1) had HLA antigen profiles that did not differ significantly from those of control fertile couples or from observed antigen frequencies in North American Caucasians; (2) shared more HLA A, B, D/DR, and MT antigens with their spouses than controls; (3) were not more hyporesponsive in MLR to paternal antigens pre- and post-immunization when compared to controls; (4) failed to develop female serum MLR blocking factors post-immunization; (5) failed to develop humoral alloantibodies to B-cell alloantigens; (5) had lymphocytes in the uterine decidua mantling the conceptus and in the uterine lymphatics that were reactive/cytotoxic to paternal stimulating alloantigens. These results are in sharp contrast to the immunodynamics of peripheral blood leukocytes and decidual leukocytes to paternal alloantigens in women who delivered infants at term post-immunization.

Abortion, Habitual↗
PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University M&#xfc;nster.

Journal Article↗
PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University M&#xfc;nster.

Journal Article↗
PubMed2005

The effects of conjugated linoleic acid on human health-related outcomes.

Conjugated linoleic acid (CLA) is a collective term for a mixture of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has received considerable attention as a result of animal experiments that report anti-carcinogenic, anti-atherogenic and anti-diabetic properties, and modulation of body composition and immune function. Several studies of CLA supplementation in human subjects have now been published, but in contrast to animal studies there has been marked variation between reports on the health-related outcomes. The consensus from seventeen published studies in human subjects is that CLA does not affect body weight or body composition. Some detrimental effects of the trans-10,cis-12 CLA isomer have also been reported in terms of altered blood lipid composition and impaired insulin sensitivity. Finally, CLA has only limited effects on immune functions in man. However, there have been reports of some interesting isomer-specific effects of CLA on the blood lipid profile, but not on immune function. These isomer-specific effects need further investigation. Until more is known, CLA supplementation in man should be considered with caution.

Animals↗
PubMed2026

Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans↗
PubMed2002

Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells.

Glucocorticoids continue to be the major immunomodulatory agents used in clinical medicine today. However, their actions as anti-inflammatory and immunosuppressive drugs are both beneficial and deleterious. We analyzed the effect of glucocorticoids on the gene expression profile of peripheral blood mononuclear cells from healthy donors. DNA microarray analysis combined with quantitative TaqMan PCR and flow cytometry revealed that glucocorticoids induced the expression of chemokine, cytokine, and complement family members as well as of newly discovered innate immune-related genes, including scavenger and Toll-like receptors. In contrast, glucocorticoids repressed the expression of adaptive immune-related genes. Simultaneous inhibitory and stimulatory effects of glucocorticoids were found on inflammatory T helper subsets and apoptosis-related gene clusters. In cells activated by T cell receptor cross-linking, glucocorticoids down-regulated the expression of specific genes that were previously up-regulated in resting cells, suggesting a potential new mechanism by which they exert positive and negative effects. Considering the broad and continuously renewed interest in glucocorticoid therapy, the profiles we describe here will be useful in designing more specific and efficient treatment strategies.

Anti-Inflammatory Agents↗