Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (810 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of t-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Agents, Immunosuppressive; Immunosuppressive Agent; Agent, Immunosuppressive; Immunosuppressant; Immunosuppressants.
Where it fits in the MeSH classification
- Broader topics
- Immunologic Factors
- Narrower topics
- Complement Inactivating Agents; Interleukin Inhibitors; MTOR Inhibitors; Myeloablative Agonists; Sphingosine 1 Phosphate Receptor Modulators
- See also
- Antilymphocyte Serum; Antirheumatic Agents
Related concepts
- T-Lymphocytes
- Helper Cells
- Interleukins
- Cytokines
Research landscape
PubMed indexes 118,410 records tagged with the MeSH heading “Immunosuppressive Agents” (counts retrieved 2026-10-29). 18,647 of them (15.7%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 39,113 records.
Reviews account for 22,911 records (19.3%) and meta-analyses for 1,216. Randomized controlled trials number 4,963 (4.2%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 25,170 |
| 2000-2009 | 35,480 |
| 2010-2019 | 39,113 |
| 2020 onward | 18,647 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 22,911 | 19.3% |
| Meta-analyses | 1,216 | 1.0% |
| Randomized controlled trials | 4,963 | 4.2% |
Method: PubMed query "Immunosuppressive Agents"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in pharmacology
Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Interactions Between Immunosuppressive Regimens and Cytomegalovirus Infection After Solid-Organ Transplantation | 2026 | Review article Design not recorded in structured metadata | 4 | cc by PMID 42040200 · DOI · PMC13102634 |
| Treatment-free remission in MS: long-term disease control with cladribine tablets | 2026 | Review article Design not recorded in structured metadata | 3 | cc by PMID 41844910 · DOI · PMC12996015 |
| Interleukin 6 as a Treatment Target for Depression: A Proof-of-Concept Randomized Clinical Trial | 2026 | Randomized controlled trial Design not recorded in structured metadata | 2 | cc by PMID 42160062 · DOI · PMC13191455 |
Interactions Between Immunosuppressive Regimens and Cytomegalovirus Infection After Solid-Organ Transplantation [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Cytomegalovirus (CMV) remains a major infectious complication after solid-organ transplantation, driven by immunosuppressive therapies that alter CMV-specific cell-mediated immunity.
- Closing excerpt
- Integrating immune monitoring tools, such as CMV-specific T-cell assays, could enable tailored immunosuppressive regimens balancing antiviral protection with graft survival.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (158 words)
Cytomegalovirus (CMV) remains a major infectious complication after solid-organ transplantation, driven by immunosuppressive therapies that alter CMV-specific cell-mediated immunity. Antithymocyte globulin induces profound and prolonged T-cell depletion, transiently impairing CMV-specific cell-mediated immunity and increasing CMV risk in seropositive recipients. Calcineurin inhibitors suppress cytokine production, notably IL-2 and IFN-γ, without significantly impairing cytotoxic function, while mycophenolate mofetil limits lymphocyte proliferation but preserves effector capacity. In contrast, mTOR inhibitors exert dual antiviral and immunomodulatory effects by directly inhibiting CMV replication and enhancing CMV-specific T-cell memory formation. Belatacept, through CD28-CD80/CD86 blockade, may predispose to late, severe, or relapsing CMV disease, particularly in elderly or D+/R- recipients. Corticosteroids broadly inhibit NK cell cytotoxicity and CMV-specific T-cell responses, but clinical data on steroid withdrawal remain inconsistent. Overall, CMV risk is determined less by a single drug than by the cumulative depth of immunosuppression. Integrating immune monitoring tools, such as CMV-specific T-cell assays, could enable tailored immunosuppressive regimens balancing antiviral protection with graft survival.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42040200 · DOI · PMC13102634
Treatment-free remission in MS: long-term disease control with cladribine tablets [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Oral cladribine, a highly effective pulsed selective immune reconstitution therapy (SIRT) for relapsing multiple sclerosis (RMS) is characterised by extended treatment-free periods following brief exposure to medication.
- Closing excerpt
- Overall, cladribine tablets show potential of a paradigmatic shift in MS management that may enable treatment-free remission over 6 years as an achievable treatment goal in a substantial proportion of RMS patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (215 words)
Oral cladribine, a highly effective pulsed selective immune reconstitution therapy (SIRT) for relapsing multiple sclerosis (RMS) is characterised by extended treatment-free periods following brief exposure to medication. Since approval in 2017, long-term real-world data have become available which provide insight into the management of patients treated with cladribine tablets beyond year 4. Most patients remained without additional therapy, which may hint at stable disease control. However, the absence of further treatment must not necessarily be interpreted as absence of any disease activity, as MRI data are often incomplete in watch-and-wait cohorts. The observed long-term remission is likely linked to the unique mode of action, which involves rapid repopulation of lymphocytes with different dynamics amongst subsets and sustained reduction of memory B cells. The recovery of the immune system and lymphocytes preserves long-term therapeutic options with existing or upcoming drugs. In cases of mild recurring disease activity, retreatment with cladribine tablets has been shown to be effective and tolerable within the known safety profile. Unrestricted long-term management options associated with cladribine tablets include a switch to other DMTs in cases of insufficient disease control. Overall, cladribine tablets show potential of a paradigmatic shift in MS management that may enable treatment-free remission over 6 years as an achievable treatment goal in a substantial proportion of RMS patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41844910 · DOI · PMC12996015
Interleukin 6 as a Treatment Target for Depression: A Proof-of-Concept Randomized Clinical Trial [3]
Abstract reading summary — source excerpts
- Opening excerpt
- ImportanceInterleukin 6 (IL-6), a keystone inflammatory cytokine, is a credible mechanistic candidate for causing depression.
- Closing excerpt
- org Identifier: ISRCTN16942542.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (437 words)
ImportanceInterleukin 6 (IL-6), a keystone inflammatory cytokine, is a credible mechanistic candidate for causing depression. However, randomized clinical trials testing its treatment potential remain scarce.ObjectiveTo identify likely treatment-sensitive outcomes and effect size for systemic IL-6 inhibition in patients with difficult-to-treat depression.Design, setting, and participantsThis 4-week, proof-of-concept, double-blind, parallel-arm, placebo-controlled randomized clinical trial recruited adults with moderate-to-severe International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) depression, poor antidepressant response, low-grade systemic inflammation (high-sensitivity C-reactive protein [hs-CRP] level ≥0.3 mg/dL on 2 tests), and depression somatic symptoms (Beck Depression Inventory II somatic symptoms score ≥7) from primary and secondary care and self-referral from 2018 to 2022. Participants were randomized into minimization balanced groups on depression severity and sex. Assessments were conducted at baseline and 7, 14, and 28 days after infusion. Data were analyzed from 2023 to 2025.InterventionSingle intravenous infusion of IL-6R antagonist tocilizumab (8 mg/kg, maximum 800 mg/patient) or normal saline.Main outcomes and measuresThe primary outcome was depression somatic symptoms at 14 days after infusion. The secondary outcome was total depression severity. Exploratory outcomes included fatigue, anxiety, anhedonia, quality of life, and cognition. Outcomes were assessed using validated scales and interpreted against clinically meaningful thresholds.ResultsA total of 30 participants (mean [SD] age, 41.1 [12.3] years; 24 [80.0%] female) were randomized, including 14 in the tocilizumab group and 16 in the placebo group. Of these, 29 participants received the assigned infusion and completed follow-up. As expected for a small proof-of-concept study, no results reached statistical significance, including little improvement in depression somatic symptoms at day 14 (adjusted mean difference: -0.12; 95% CI, -2.51 to 2.28). However, a pattern of greater stepwise improvement over time was observed with tocilizumab in somatic symptoms, depression severity, fatigue, psychological symptoms, state anxiety, and quality of life, with the largest effects observed at the final follow-up (day 28). Tocilizumab may also improve more individual depressive symptoms. Treatment effects were within ranges considered clinically meaningful for depression severity, fatigue, anxiety, and quality of life. At the final follow-up, remission (7 participants [53.9%] vs 5 participants [31.3%]; number needed to treat [NNT] = 5) and response (6 participants [46.2%] vs 3 participants [18.8%]; NNT = 4) rates favored tocilizumab compared with placebo. Baseline hs-CRP level, but not IL-6 level, tracked depression improvement, suggesting hs-CRP may better predict immunotherapy response in depression than drug-specific biomarkers. Tocilizumab was well tolerated, with no serious adverse events or withdrawals.Conclusions and relevanceThese findings highlight treatment-sensitive outcomes, effect sizes, and patient selection methods for testing systemic IL-6 inhibition in patients with difficult-to-treat depression, and call for a large-scale efficacy trial of anti-IL-6 treatment in depression.Trial registrationisrctn.org Identifier: ISRCTN16942542.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42160062 · DOI · PMC13191455
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis [4]
- Research article Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials [5]
- Research article Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis [6]
- Research article Ruxolitinib-associated infections: A systematic review and meta-analysis [7]
- Research article Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis [8]
- Research article Systematic Review and Meta-Analysis: Infliximab or Cyclosporine as Rescue Therapy in Patients With Severe Ulcerative Colitis Refractory to Steroids [9]
References
- Bellier LM, Kaminski H, Merville P, Couzi L. Interactions Between Immunosuppressive Regimens and Cytomegalovirus Infection After Solid-Organ Transplantation. . 2026. PMID 42040200 · DOI · PMC13102634
- Wiendl H, Gold R, Pul R, Ernst M, Kowarik MC, Klehmet J, et al.. Treatment-free remission in MS: long-term disease control with cladribine tablets. . 2026. PMID 41844910 · DOI · PMC12996015
- Foley ÉM, Turner N, Margelyte R, Jones HJ, Kaser M, Lewis G, et al.. Interleukin 6 as a Treatment Target for Depression: A Proof-of-Concept Randomized Clinical Trial. . 2026. PMID 42160062 · DOI · PMC13191455
- WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, et al.. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis. JAMA. 2021. PMID 34228774 · DOI · PMC8261689
- Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, et al.. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020. PMID 32446407 · DOI · PMC7613154
- Kotlyar DS, Lewis JD, Beaugerie L, Tierney A, Brensinger CM, Gisbert JP, et al.. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol. 2015. PMID 24879926 · DOI
- Lussana F, Cattaneo M, Rambaldi A, Squizzato A. Ruxolitinib-associated infections: A systematic review and meta-analysis. Am J Hematol. 2018. PMID 29150886 · DOI
- Singh S, Facciorusso A, Dulai PS, Jairath V, Sandborn WJ. Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2020. PMID 30876964 · DOI · PMC8011651
- Narula N, Marshall JK, Colombel JF, Leontiadis GI, Williams JG, Muqtadir Z, et al.. Systematic Review and Meta-Analysis: Infliximab or Cyclosporine as Rescue Therapy in Patients With Severe Ulcerative Colitis Refractory to Steroids. Am J Gastroenterol. 2016. PMID 26856754 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.