Effects of long‐term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma

Uhlig, Torsten; Cooper, David K. C.; Eber, Ernst; McMenamin, Christine; Wildhaber, Johannes H.; Sly, Peter D.

doi:10.1046/j.1365-2222.1998.00309.x

Cited by 7 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the rat, Th1 cytokines favor the generation of IgG2a and IgG2b immunoglobulins, whereas under the influence of Th2 cytokines, IgG1 antibodies are preferentially produced. 47,48 Similar to our findings in the EAE model, lymph node T cells from superTGR rats secreted high levels of IL-4 and reduced amounts of IFN␥ after intranasal challenge with ovalbumin (data not shown). To investigate whether this Th2 bias impacts the production of ovalbumin-specific antibodies, we followed their time course in the serum over the time period of immunization.…”

Section: Isotype Switching Is Altered In Supertgr Ratssupporting

confidence: 83%

“…In contrast, superTGR rats completely failed to produce any antigen-specific IgG2a and IgG2b immunoglobulins, two Th1-specific antibody classes. 47 The previous finding in mice that IL-4 was able to suppress IgG2a and IgG2b class-switching provides a convincing explanation for this observation. 53 We predict that the altered antibody class profile following enhanced GR signaling may significantly influence the quality of an immune response.…”

Section: Discussionmentioning

confidence: 81%

See 1 more Smart Citation

Enhanced Glucocorticoid Receptor Signaling in T Cells Impacts Thymocyte Apoptosis and Adaptive Immune Responses

Brandt

Lühder

McPherson

et al. 2007

The American Journal of Pathology

View full text Add to dashboard Cite

To study the effect of enhanced glucocorticoid signaling on T cells, we generated transgenic rats overexpressing a mutant glucocorticoid receptor with increased ligand affinity in the thymus. We found that this caused massive thymocyte apoptosis at physiological hormone levels, which could be reversed by adrenalectomy. Due to homeostatic proliferation, a considerable number of mature T lymphocytes accumulated in the periphery, responding normally to costimulation but exhibiting a perturbed T-cell repertoire. Furthermore, the transgenic rats showed increased resistance to experimental autoimmune encephalomyelitis, which manifests in a delayed onset and milder disease course, impaired leukocyte infiltration into the central nervous system and a distinct cytokine profile. In contrast, the ability of the transgenic rats to mount an allergic airway response to ovalbumin was not compromised, although isotype switching of antigen-specific immunoglobulins was altered. Collectively, our findings suggest that endogenous glucocorticoids impact T-cell development and favor the selection of Th2- over Th1-dominated adaptive immune responses.

show abstract

Section: Isotype Switching Is Altered In Supertgr Ratssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 81%

Enhanced Glucocorticoid Receptor Signaling in T Cells Impacts Thymocyte Apoptosis and Adaptive Immune Responses

Brandt

Lühder

McPherson

et al. 2007

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…However, the effects of these disease-modifying drugs and immunosuppressant on airway hyperresponsiveness and asthma were controversial. A few experimental studies demonstrated the attenuation of allergen-induced airway inflammation and sensitization after long-term use of leflunomide 32,33 . In addition, immunosuppressant was suggested to relieving asthma by inhibition of T cell activation 34 .…”

Section: Discussionmentioning

confidence: 99%

Increased risk of asthma in patients with rheumatoid arthritis: A longitudinal follow-up study using a national sample cohort

Kim

Min

et al. 2019

Sci Rep

View full text Add to dashboard Cite

The aim of this study was to evaluate the risk of asthma in rheumatoid arthritis patients using matched control group for socioeconomic factors and past medical history. Adults >20 years old were collected from the Korean Health Insurance Review and Assessment Service - National Sample Cohort (HIRA-NSC) from 2002 through 2013. A total of 6,695 individuals with rheumatoid arthritis were matched for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 26,780 individuals included in a control group. In both the rheumatoid arthritis and control groups, subjects’ history of asthma was evaluated. Asthma (J45 and J46) and rheumatoid arthritis (M05 and M06) were included based on the International Classification of Disease-10 (ICD-10) codes and medication history. The crude and adjusted (depression and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CI) of asthma for rheumatoid arthritis patients were analyzed using a stratified Cox proportional hazard model. Subgroup analyses were conducted according to age and sex, number of treatment histories, and medication histories. Approximately 16.4% (1,095/6,695) of rheumatoid arthritis group and 13.0% (3,469/26,780) of the control group had asthma (P < 0.001). The rheumatoid arthritis group demonstrated a higher adjusted HR for asthma than the control group (adjusted HR = 1.23, 95% CI = 1.15–1.32, P < 0.001). This result was consistent in all subgroups. Rheumatoid arthritis was related to an increase risk of asthma.

show abstract

Effects of Drugs on Air Ways

Bruse¹

2016

Drug Discovery and Evaluation: Pharmacological Assays

View full text Add to dashboard Cite

Effects of long‐term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma

Abstract: Leflunomide prevents antigen-specific immunoglobulin production after sensitization during treatment, inhibits allergen-induced airway inflammation and diminishes antigen-specific T lymphocyte proliferation.

Cited by 7 publications

References 27 publications

Enhanced Glucocorticoid Receptor Signaling in T Cells Impacts Thymocyte Apoptosis and Adaptive Immune Responses

Enhanced Glucocorticoid Receptor Signaling in T Cells Impacts Thymocyte Apoptosis and Adaptive Immune Responses

Increased risk of asthma in patients with rheumatoid arthritis: A longitudinal follow-up study using a national sample cohort

Effects of Drugs on Air Ways

Contact Info

Product

Resources

About