作者: van den Boogaard, Mark ; van Gelder, Thomas G ; van Diem-Zaal, Irene J ; Zegers, Marieke ; Slooter, Arjen J C ; Lalmohamed, Arief ; Egberts, Toine C G

OBJECTIVE:

To assess whether exposure to interleukin-6 (IL-6) inhibitors as treatment for critically ill COVID-19 patients is associated with a lower prevalence of mental health problems one year after ICU admission.

DESIGN:

Retrospective cohort study using prospectively collected outcome data.

SETTING:

Two university medical centers in the Netherlands: University Medical Center Utrecht (UMCU) and Radboud University Medical Center (Radboudumc).

PATIENTS:

Adult ICU survivors admitted to the ICU for COVID-19 from September 1, 2020, to March 31, 2022, with available one-year follow-up data.

EXPOSURE:

IL-6 inhibitors (tocilizumab or sarilumab) as treatment for COVID-19.

MEASUREMENTS AND MAIN RESULTS:

Mental health problems were assessed using the Impact of Event Scale (IES-6 or IES-R) for post-traumatic stress disorder (PTSD) and the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression. The primary outcome was a composite of PTSD, anxiety, and/or depression symptoms one year after ICU admission. Among 170 patients included in the primary analysis (119 exposed to IL-6 inhibitors, 51 unexposed), IL-6 inhibitor exposure was associated with a lower prevalence of mental health problems (adjusted odds ratio (aOR) 0.46, 95% confidence interval (CI) 0.22-0.93) and PTSD symptoms alone (aOR 0.45, 95% CI 0.20-0.97). No significant associations were found for anxiety (aOR 0.77, 95% CI 0.34-1.72) or depression (aOR 0.71, 95% CI 0.33-1.50) symptoms alone.

CONCLUSIONS:

Exposure to IL-6 inhibitors as treatment for critically ill COVID-19 patients was associated with a lower prevalence of mental health problems, primarily driven by a lower prevalence of PTSD symptoms, one year after ICU admission. These findings suggest a potential role for cytokine-targeted therapies in mitigating long-term mental health problems in ICU survivors, but further research is needed to establish causality.

KEY POINTS:

Question: Does treatment with interleukin-6 (IL-6) inhibitors during ICU admission for COVID-19 reduce the prevalence of mental health problems one year later?

FINDINGS:

In this multicenter cohort study of 170 COVID-19 ICU survivors, IL-6 inhibitor exposure was associated with a significantly lower prevalence of PTSD and of the composite outcome of PTSD, anxiety, or depression symptoms one year after ICU admission. Meaning: These findings suggest that IL-6 inhibition during critical illness may help mitigate long-term psychological burden in ICU survivors.

2026-08-01·CYTOKINE

TGF-beta inhibitors influence leishmania infection outcome in a susceptible host

Article

作者: Pal, Chiranjib ; Gurjar, Dhiraj ; Bodhale, Neelam ; Ray, Monalisa ; Barik, Susmita ; Nanda, Prakash Kumar ; Saha, Bhaskar ; Sarkar, Arup

Transforming growth factor-β (TGF-β) is a key immunoregulatory cytokine that promotes parasite persistence in macrophages, immunosuppression by deactivation of macrophages and regulatory T cell differentiation and Th17-mediated pathogenesis in leishmaniasis. Targeting TGF-β signaling therefore represents a promising host-directed therapeutic approach. Herein, we investigated the therapeutic potential of pharmacological inhibitors targeting the TGF-β receptor and signaling pathway in vitro and in susceptible BALB/c mice in an experimental model of visceral leishmaniasis. BALB/c-derived peritoneal macrophages were infected with L. donovani promastigotes and treated with salirasib- a Ras inhibitor, angoline- an IL-6 inhibitor, SIS3- a SMAD3 inhibitor, or galunisertib- a TGF-β receptor inhibitor. Parasite burden and nitric oxide (NO) production were quantified, and cytokine responses were analyzed. While salirasib elevated NO production without reducing parasite load, and angoline failed to show significant effects, galunisertib markedly reduced intracellular amastigotes and enhanced NO levels. SIS3 alone induced modest cytokine alterations without significantly reducing parasite burden. Infected BALB/c mice treated with galunisertib significantly reduced hepatic and splenic parasite burdens, measured as Leishman-Donovan Units (LDUs). Cytokine profiling revealed that Galunisertib enhanced pro-inflammatory cytokines (IL-12, TNF-α, IFN-γ, IL-17) and downregulated TGF-β, whereas SIS3 selectively increased IL-12 and TNF-α while reducing IL-10. Combined galunisertib and SIS3 treatment synergistically increased both pro-inflammatory and anti-inflammatory cytokines, notably IL-10, which may offset parasite clearance. These findings establish TGF-β receptor inhibition as a promising host-directed therapeutic approach against visceral leishmaniasis, while highlighting the immunoregulatory complexities of targeting TGF-β signaling.

2026-07-01·AMERICAN JOURNAL OF TRANSPLANTATION

Regulatory T cell modulation with selective CD28 blockade and IL-6 receptor antagonist in kidney transplant recipients: Results of CTOT-24—a prospective clinical trial

Article

作者: Armstrong, Brian D ; Tang, Qizhi ; Kirk, Allan D ; Chandran, Sindhu ; Laszik, Zoltan G ; Friedewald, John J ; Morsheimer, Megan ; Goldstein, Julia ; Vincenti, Flavio G ; Leung, Joey C

We hypothesized that combined blockade of CD28 and interleukin-6 would favor regulatory T cells (Tregs) and prevent rejection in a novel calcineurin inhibitor-free immunosuppression regimen. In CTOT-24, a multicenter, prospective, phase I/II, pilot clinical trial, live donor kidney transplant recipients received lulizumab pegol, a novel anti-CD28 domain antibody, and tocilizumab, an anti-IL-6R antibody, for 3 months followed by belatacept and tocilizumab for 3 months. All subjects received antithymocyte globulin, steroids, and mycophenolate mofetil or everolimus. The primary endpoint was the proportion of subjects free of biopsy-proven acute rejection at 6 months posttransplantation. Of 8 treated subjects, 5 discontinued the study therapy prematurely for early acute T cell-mediated rejection, severe neutropenia, and subject preference; 3 completed the regimen without rejection and remained on belatacept, mycophenolate mofetil, and prednisone with a mean estimated glomerular filtration rate of 85.63 mL/min/1.73 m² at 2 years posttransplantation. There were no cases of antibody-mediated rejection, death, or graft loss. Flow cytometric analyses showed no increase in circulating Tregs under the study regimen and no differences between rejectors and nonrejectors. We conclude that a regimen of combined CD28 and interleukin-6 blockade prevented rejection in only a minority and that alternative strategies are needed to promote Tregs under CD28 blockade. NCT04066114.

项与 IIIM-17/13 相关的新闻（医药）

2026-04-21

·FiercePharma

Roche’s Enspryng cuts relapse risk by 68% in rare neuroinflammatory disease

Roche Pharmaceuticals chief Teresa Graham has pinned 500 million Swiss francs in peak sales on a MOGAD expansion for Enspryng. The era of off-label guesswork for patients living with the rare autoimmune disorder MOGAD may soon be over, as a phase 3 victory for Roche’s Enspryng suggests a first-of-its-kind FDA approval may not be far away.Data from the phase 3 Meteoroid trial—the first randomized-controlled trial in this space—showed that Enspryng (satralizumab) reduced the risk of a MOGAD relapse by 68% versus placebo, according to results presented at the American Academy of Neurology 2026 annual meeting. MOGAD, or myelin oligodendrocyte glycoprotein antibody-associated disease, is a rare disease in which the immune system attacks the myelin sheath that protects nerve fibers, causing some of the same symptoms as multiple sclerosis, including vision loss, muscle dysfunction, seizures and headaches. Unlike from MS and another neuroinflammatory disease neuromyelitis optica spectrum disorder (NMOSD), MOGAD is characterized by the presence of MoG-IgG autoantibodies. As MOGAD is a relatively newly defined disease, no FDA-approved therapies exist. Patients are currently treated with immunosuppressants such as corticosteroids, azathioprine and mycophenolate mofetil, which are supported by empirical evidence only, Friedemann Paul, M.D., a neuroimmunology expert at Charité Universitätsmedizin Berlin, explained after sharing the Meteoroid results during a press conference. He described Enspryng’s results as “very impressive,” potentially leading to the first approved therapy to prevent attacks in MOGAD. The IL-6 receptor antagonist is already approved to treat NMOSD with AQP4 antibodies. RELATED: Roche reports another phase 3 multiple sclerosis win, but deaths add to safety questionsThe Meteoroid trial enrolled 132 patients aged 12 years and older who had experienced at least two MOGAD attacks in the past two years; they were allowed to receive background therapy of immunosuppressants during the study.The 68% reduction in new relapses was “highly statistically significant,” Paul said. Enspryng’s treatment effect started to show “fairly early on,” from about eight to 10 weeks, and the results seen between the trial arms continued to diverge over the course of the study, he added.At 48 weeks, 87% of patients in the Enspryng arm were relapse-free, compared with 67% on placebo. Outcomes from the secondary endpoints were “very consistent” with the primary endpoint, according to Paul. These measures included the annualized rate of MOGAD relapses, the annualized rate of serious attacks, active MRI lesions and the proportion of patients who received rescue therapy.On the safety side, the study recorded one patient death from malignant melanoma. But neither that nor any other serious adverse events were attributed to treatment.“The safety profile was almost exactly what we have seen in the NMOSD trials regarding the type and frequency of adverse events,” Paul said of Enspryng. Roche telegraphed the positive Meteoroid readout during its fourth-quarter earnings report in January. At that time, Roche Pharmaceuticals chief Teresa Graham said the Swiss pharma planned to file for approvals with the U.S. FDA and the European Medicines Agency in 2026, adding that the indication could unlock about 500 million Swiss francs in peak sales for Enspryng. Last year, the antibody drug grew sales by 23% at constant currencies to 364 Swiss francs.In addition to MOGAD, Roche is also eying an FDA approval for Enspryng as a treatment for thyroid eye disease and is testing the drug in a pivotal study for autoimmune encephalitis. Meanwhile, the company recently called it quits on a development program in Duchenne muscular dystrophy after struggling to recruit patients for a phase 2 trial.