RESUMEN
AIM: Much focus of immunotherapy for type 1 diabetes (T1D) has been devoted on selectively boosting regulatory T (Treg) cells using low dose IL-2 due to their constitutive expression of IL-2Rα, CD25. However, several clinical trials using a low dose of IL-2 only showed a limited improvement of metabolic control. It can therefore be hypothesized that further decreasing IL-2 dosage may increase the selective responsiveness of Treg cells. METHODS: We induced experimental T1D using multiple low dose streptozotocin (STZ) injections and treated the mice with an ultra-low dose IL-2 (uIL-2, approximately 7-fold lower than low dose). Immune response was studied using multicolor flow cytometry. RESULTS: We found that uIL-2 did not protect STZ mice from developing hyperglycemia. It did neither increase Treg cell proportions, nor did it correct the phenotypic shift of Treg cells seen in T1D. It only partially decreased the proportion of IFN-γ+ T cells. Likewise, uIL-2 also did not protect the dysfunction of regulatory B (Breg) cells. Strikingly, when administered in combination with an anti-inflammatory cytokine IL-35, uIL-2 abrogated IL-35's protective effect. Low dose IL-2, on the other hand, protected half of the STZ mice from developing hyperglycemia. No difference was found in the Treg and Breg response, and it only tended to decrease CD80 expression in macrophages and dendritic cells. CONCLUSION: In conclusion, further decreasing IL-2 dosage may not be a suitable approach for T1D therapy, and the limited success suggests that an alternative low dose IL-2 therapy strategy or other immunotherapies should be considered.
RESUMEN
Background Early epidural steroid injections are currently widely used for patients experiencing lumbago. However, there is uncertainty about their efficacy, such as the limitation of continuous drug infusion and the need for well-trained physicians on this technique. The main objective of this study was to evaluate the effectiveness of early epidural steroid injections in treating patients with acute sciatica in the lower back in terms of symptom relief and recurrence rate. Methods A case series was conducted in Lebanon from 2015 to 2019. We recruited 98 patients suffering from sciatica due to disc disease over three-time intervals: two weeks, one, and three months. The immediate results accounted for the intensity of various symptoms (numerical rating scale (NRS) for pain) and the assessment of patient satisfaction (Macnab criteria). Results The clinical results showed at least a three-point pain relief according to Numerical Rating Scale (NRS) and a good grade according to MacNab (P <0.001), with only 10.4% of the total population having a positive leg raise test post-injection. The maximum benefit was noted after two weeks from the injection with a 5.7 mean change in NRS (p<0.001) with a good/excellent response in MacNab and a 4.9 change with only a good response after one month. This study noticed a rebound phenomenon where around half of the patients needed two steroid injections after three months (39.6 % after three months and 17.9 % after six months). Conclusion Even though current guidelines worldwide may suggest the use of conservative treatment for low back pain with acute sciatica, our study has demonstrated the effectiveness of epidural steroid injections in the Lebanese population with a significant outcome.
