Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1 alpha (IL-1α) and interleukin 1 beta (IL-1β), has demonstrated promising results in a phase II study in recurrent or refractory pericarditis. Anakinra is a recombinant inhibitor of the IL-1 receptor with a demonstrated reduction in the incidence of recurrent pericarditis. Definite pharmacological management of pericarditis is key to preventing recurrences, mostly treatment options for recurrent pericarditis refractory to conventional drugs. Here we critically discuss the existing therapy options for recurrent pericarditis, with a focus on new pharmacological approaches: rilonacept and anakinra. A systematic search was conducted across online databases such as PubMed, Cochrane, Google Scholar, ScienceDirect, CINAHL, Scopus, and Embase to obtain clinical trials that assess the effectiveness of anti-interleukin 1 therapy such as anakinra and rilonacept in the management of recurrent pericarditis. Our study concluded that anti-interleukin 1 therapy significantly improved both the quality of life and the clinical outcomes of the study population. These outcomes were most prominent with the use of rilonacept and anakinra in the trial treatment. Rilonacept and anakinra are valuable options in case of recurrent pericarditis refractory to conventional drugs.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are considered as inflammasome disorders associated with uncontrolled interleukin (IL)-1β production. Anti-IL1 agents are used in colchicine-resistant cases of FMF. Increase in pro-inflammatory mediators even between febrile attacks in PFAPA suggests that anti-IL1 treatment might be beneficial in these patients. We describe a child presenting with recurrent, self-limited febrile attacks at 1 year of age who was diagnosed as FMF being heterozygous for M694 V mutation. Her clinical findings were only controlled by the addition of canakinumab (2 mg/kg/8 week) to colchicine treatment. However, she developed typical PFAPA attacks during this treatment at 3 years of age. We conducted a literature search focusing on English articles with keywords including PFAPA, anakinra, canakinumab, and rilonacept. Five children and one adult patient with PFAPA were found and evaluated. Anakinra was reported to abort PFAPA attacks in children, while the adult patient first responded and then became resistant to anakinra. Canakinumab was effective in preventing febrile attacks in this patient. Failure of canakinumab to prevent PFAPA attacks in our case may arise from the differences in the pathophysiology of PFAPA and FMF. Thus, further experience with higher doses or shorter intervals of canakinumab is needed in children with PFAPA.

Muckle-Wells syndrome (MWS) is a rare autoinflammatory disorder. It is due to NLRP3 gene mutations, responsible for excessive caspase-1 activation and interleukin 1β processing. MWS is the intermediate phenotype of severity of cryopyrin-associated periodic syndrome. Urticarial rash, conjunctivitis, recurrent fever, arthralgia, and fatigue are the main clinical manifestations of MWS. Yet, sensorineural hearing loss and renal amyloidosis can occur after long term evolution. Patients\' quality of life has been drastically improved with the advent of IL-1 inhibitors. This review reports recent findings in MWS, particularly genotype/phenotype correlation, and discusses the clinical perspectives of this disease in a time of efficient treatment.

BACKGROUND: Amyloidosis may complicate autoinflammatory diseases (AID). We aimed to evaluate the renal biopsy findings, and clinical and laboratory parameters in patients with AID-associated amyloidosis who have responded to anti-interleukin 1(IL1) treatment.
METHODS: Two children with systemic juvenile idiopathic arthritis and one with cryopyrin-associated periodic syndrome diagnosed as having reactive amyloidosis were treated with anti-IL1 drugs. The renal histopathological findings at the time of diagnosis of amyloidosis and after the onset of anti-IL1 were evaluated according to the amyloid scoring/grading system.
RESULTS: The median age of disease onset and diagnosis of amyloidosis were 3 and 12 years, respectively. Anakinra was started in all; however, anakinra caused a local cutaneous reaction in one, thus canakinumab was commenced. Proteinuria improved in all. Control renal biopsies were performed a median of 3 years after the first biopsies. The renal amyloid prognostic score did not improve in patient 1, and progressed in patients 2 and 3. The renal amyloid grade progressed in patient 2.
CONCLUSIONS: This is the first series demonstrating progression of renal tissue damage after the improvement of proteinuria with anti-IL 1 in AID-associated amyloidosis. Anti-IL1 drugs are important to prevent further amyloid accumulation; however, new treatment strategies are needed to target the amyloid deposits.

Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future.