Background: For thousands of years till nowadays, Nigella sativa (NS) has served as a common spice and food preservative. Its seed extracts, seed oil, and essential oil in traditional medicine have been used to remedy many ailments such as headaches, fever, gastric complaints, and even rheumatism. In addition, the antibacterial, virucidal, fungicidal, and antiparasitic properties of NS are well known. However, studies on the possible immunomodulatory effects of black cumin are relatively scarce. This article discusses in vitro and in vivo research supporting the immunomodulatory role of NS. Methods: The review is based on articles, books, and conference papers printed until September 2022, found in the Web of Science, PubMed, Wiley Online Library, and Google Scholar databases. Results: Experimental findings were reported concerning the ability of NS to modulate inflammation and immune responses or cytotoxic activity. Conclusions: All results suggest that NS can potentially be employed in developing effective therapeutic agents for regulating immune reactions.

The CD28 family receptors include the CD28, ICOS (inducible co-stimulator), CTLA-4 (cytotoxic T-lymphocyte antigen-4), PD-1 (programmed cell death protein 1), and BTLA (B- and T-lymphocyte attenuator) molecules. They characterize a group of molecules similar to immunoglobulins that control the immune response through modulating T-cell activity. Among the family members, CD28 and ICOS act as enhancers of T-cell activity, while three others—BTLA, CTLA-4, and PD-1—function as suppressors. The receptors of the CD28 family interact with the B7 family of ligands. The cooperation between these molecules is essential for controlling the course of the adaptive response, but it also significantly impacts the development of immune-related diseases. This review introduces the reader to the molecular basis of the functioning of CD28 family receptors and their impact on T-cell activity.

Rhododendron tomentosum (Ledum palustre) is an aromatic plant traditionally used for alleviating rheumatic complaints which makes it a potential candidate for a natural drug in rheumatoid arthritis (RA) treatment. However, the effects of plants' volatiles on apoptosis of synovial fibroblasts and infiltrating leucocytes of RA synovia, have not been reported. Volatile fraction of R. tomentosum is chemically variable and chemotypes of the plants need to be defined if the oil is to be used for therapeutic purposes. In the presented work, cluster analysis of literature data enabled to define 10 chemotypes of the plant. The volatile fractions of known composition were then tested for bioactivity using a RA-specific in vitro models. Essential oils of two wild types (γ-terpineol and palustrol/ledol type) and one in vitro chemotype (ledene oxide type) were obtained by hydrodistillation and their bioactivity was tested in two in vitro models: I - peripheral blood lymphocytes of healthy volunteers and II - synoviocytes and immune cells isolated from synovia of RA patients. The influence of oils on blood lymphocytes' proliferation and apoptosis rates of synovia-derived cells was determined by flow cytometry. Dose-dependent inhibitory effect of the serial dilutions of R. tomentosum oils on proliferation rates of blood lymphocytes was found. At 1:400 dilutions, all the tested oils increased the number of necrotic cells in synovial fibroblasts from RA synovia. Additionally, increased proportions of late apoptotic cells were observed in leucocyte populations subjected to oils at 1:400 dilution.

Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease mediated by T cells. It is characterized by the presence of thyroid autoantibodies in the serum, such as anti-thyroid peroxidase antibodies (TPO-Ab) and anti-thyroglobulin antibodies (TG-Ab). The essential oil extracted from Nigella sativa seeds is rich in bioactive substances, such as thymoquinone and cymene. Methods: Therefore, we examined the effect of essential oil from Nigella sativa (NSEO) on T cells from HT patients, especially their proliferation capacity, ability to produce cytokines, and susceptibility to apoptosis. Results: The lowest ethanol (EtOH) dilution (1:10) of NSEO significantly inhibited the proliferation of CD4⁺ and CD8⁺ T cells from HT patients and healthy women by affecting the percentage of dividing cells and the number of cell divisions. In addition, 1:10 and 1:50 NSEO dilutions induced cell death. Different dilutions of NSEO also reduced the concentration of IL-17A and IL-10. In healthy women, the level of IL-4 and IL-2 significantly increased in the presence of 1:10 and 1:50 NSEO dilutions. NSEO did not influence the concentration of IL-6 and IFN-γ. Conclusions: Our study demonstrates that NSEO has a strong immunomodulatory effect on the lymphocytes of HT patients.

Treatment-resistant depression (TRD) is associated with immune dysregulation. Ketamine, a rapid-acting antidepressant, may exert effects via immunomodulation. The aim was to examine ketamine’s impact on immune markers in TRD, including T-cell subsets, cytokines, and in vitro T-cell responses. Eighteen TRD inpatients received 0.5 mg/kg iv ketamine. Blood was sampled at baseline, 4 h, and 24 h to analyze T-cell phenotypes (CD28, CD69, CD25, CD95, HLA-DR) and serum cytokines (IL-6, IL-8, IL-10, TNF-α, IL-1β, IL-12p70). In vitro, PBMCs from TRD patients and controls were exposed to low (185 ng/mL) and high (300 ng/mL) ketamine doses. Ketamine induced a transient increase in total T cells and CD4⁺CD25⁺ and CD4⁺CD28⁺ subsets at 4 h, followed by a reduction in CD4⁺ and an increase in CD8⁺ T cells at 24 h, decreasing the CD4⁺/CD8⁺ ratio. Activation markers (CD4⁺CD69⁺, CD4⁺HLA-DR⁺, CD8⁺CD25⁺, CD8⁺HLA-DR⁺) declined at 24 h. Serum IL-10 increased, IL-6 decreased, and IL-8 levels—initially elevated—showed a sustained reduction. In vitro, high-dose ketamine enhanced the proliferation of TRD CD4⁺ T cells and dose-dependent IL-8 and IL-6 secretion from activated cells. Ketamine induces rapid, transient immune changes in TRD, including reduced T-cell activation and cytokine modulation. A sustained IL-8 decrease suggests anti-inflammatory effects and potential as a treatment-response biomarker.

Systemic lupus erythematosus (SLE) patients have an increased risk of infections and infection-related mortality. Therefore, during the global SARS-CoV-2 pandemic, SLE patients were particularly vulnerable to SARS-CoV-2 infections. Also, compared to other patients, SLE patients seem to develop more severe manifestations of coronavirus disease 2019 (COVID-19), with higher rates of hospitalization, invasive ventilation requirements, or death. This study evaluated the immune parameters after SARS-CoV-2 infection in SLE patients. We analyzed subpopulations of peripheral blood cells collected from patients with renal manifestation of SLE (lupus nephritis, LN). LN patients were divided into two subgroups: those unexposed to SARS-CoV-2 (LN CoV-2(−)) and those who had confirmed COVID-19 (LN-CoV-2(+)) six months earlier. We analyzed basic subpopulations of T cells, B cells, monocytes, dendritic cells (DCs), and serum cytokines using flow cytometry. All collected data were compared to a healthy control group without SARS-CoV-2 infection in medical history. LN patients were characterized by a decreased percentage of helper T (Th) cells and an increased percentage of cytotoxic T (Tc) cells regardless of SARS-CoV-2 infection. LN CoV-2(+) patients had a higher percentage of regulatory T cells (Tregs) and plasmablasts (PBs) and a lower percentage of non-switched memory (NSM) B cells compared to LN CoV-2(−) patients or healthy controls (HC CoV-2(−)). LN patients had a higher percentage of total monocytes compared with HC CoV-2(−). LN CoV-2(+) patients had a higher percentage of classical and intermediate monocytes than LN CoV-2(−) patients and HC CoV-2(−). LN CoV-2(+) patients had higher serum IL-6 levels than HC CoV-2(−), while LN CoV-2(−) patients had higher levels of serum IL-10. LN patients are characterized by disturbances in the blood’s basic immunological parameters. However, SARS-CoV-2 infection influences B-cell and monocyte compartments.