サラゾスルファピリジン（Sulfasalazine）は、炎症性疾患の治療において、IL-1シグナルを含む炎症性サイトカインの抑制を通じて抗炎症作用を発揮します。そのメカニズムは以下のように考えられています： サイトカインの遊離抑制: サラゾスルファピリジンは、マクロファージやT細胞からのIL-1、IL-2、IL-6などの炎症性サイトカインの遊離を抑制します。これにより、炎症反応が軽減されます。 NF-κB経路の抑制: サラゾスルファピリジンは、NF-κB（核因子カッパB）という転写因子の活性化を抑制することで、炎症性遺伝子の発現を抑えます。この経路はIL-1シグナル伝達において重要な役割を果たします。 抗酸化作用: サラゾスルファピリジンの代謝物である5-アミノサリチル酸（5-ASA）は、活性酸素種（ROS）の生成を抑制し、炎症部位での酸化ストレスを軽減します。 これらの作用により、サラゾスルファピリジンは関節リウマチや潰瘍性大腸炎などの治療に有効とされています。 Abstract In an open study, 32 patients with moderate to severe stable plaque psoriasis were treated with sulfasalazine, 3 gm daily for 8 weeks. Twenty-four patients completed the study, and 19 had modest to marked improvement or clearing. If confirmed by a double-blind study, sulfasalazine could become an alternative therapy in some patients with moderate to severe psoriasis. 1. Introduction Inflammation is a physiological process that controls pathogen invasion and promotes tissue repair. This process might become pathological when exacerbated or when its regulatory mechanisms are altered [1]. Some infectious agents, such as the human immunodeficiency virus type 1 (HIV-1), can exacerbate the inflammatory response, thereby leading to the progressive loss of the functional capacity of the immune system [2]. This phenomenon affects different cellular subpopulations, including monocytes/macrophages and dendritic cells, which are activated upon recognition of microbial products through pattern recognition receptors, such as Toll-like receptors (TLRs) and nucleotide-binding domain (NOD)-like receptors (NLRs) [3,4]. This process induces the expression of pro-inflammatory cytokines such as IL-1β and IL-18, which in turn promotes the differentiation and proliferation of naïve CD4+ T lymphocytes toward the main HIV-1 targets, i.e., the Th1 and Th17 cells [5,6,7,8]. Particularly, some innate sensors assemble with the adaptor protein ASC and pro-caspase-1 into multi-molecular complexes called inflammasomes [9,10]. Once such complexes activate caspase-1, IL-1β and IL-18 undergo proteolytic maturation and are then released, thus inducing inflammatory effects and pyroptosis, an inflammatory type of cell death [11,12]. To date, five inflammasomes have been characterized, namely NLRP1, NLRP3, NLRC4 (belonging to the NLR family), AIM2, and the recently described Pyrin [13]. They are activated in response to different stimuli, including infectious agents and changes in cell homeostasis. It has been previously demonstrated that HIV-1 promotes the activation of inflammasomes [14]. Moreover, people living with HIV who naturally control viral replication, known as HIV-controllers, exhibit a lower expression of inflammasome-related genes, such as IL-1β, IL-18, and caspase-1, and a lower production of IL-1β through NLRP1, NLRC4, and AIM2 inflammasomes in the gut-associated lymphoid tissue (GALT) and peripheral blood mononuclear cells (PBMCs), compared to HIV- progressors [15]. These results suggest that inflammasomes could be involved in pathogenesis and disease progression in people living with HIV. Therefore, the search for therapies modulating this inflammatory process constitutes an important field of research. In this sense, sulfasalazine (SSZ), an anti-inflammatory agent that combines the antibiotic sulphapyridine with 5-aminosalicylic acid [16], might exert its action by inhibiting inflammasomes. To date, studies have demonstrated that SSZ improves the clinical symptoms of rheumatic diseases such as spondyloarthropathy and Reiter’s syndrome [17,18], while a beneficial effect during HIV-infection has also been proposed but with no experimental evidence underlying this claim. In addition, the mechanisms involved in the immunomodulatory action of SSZ remain unknown. In this sense, the present study aimed to evaluate the potential inhibitory effect of SSZ on inflammasomes and TLR activity, by measuring the release of IL-1β, and the mRNA expression of the inflammasome-related genes in PBMCs, from people living with HIV and healthy donors.