Objective To discuss the relationship between adipokines and connective tissue diseases, by putting special emphasis on the potential role of leptin, adiponectin, resistin, and other adipose tissue products in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus and on possible application of adipokine-targeted therapy in the treatment of these disorders with emphasis on the recent findings. Methods PubMed literature search complemented by review of bibliographies listed in identified articles. Results Most of the data presented by different research groups showed changed levels of leptin, adiponectin, and resistin and occasionally also other adpokines in rheumatoid arthritis and systemic lupus erythematosus. The relationship between the remaining connective tissue diseases and adipokines is less documented. Conclusions Plasma levels of adipokines might tell us too little about their role in connective tissue disorders, whereas adipokine effects on synovial tissues might differ from their known metabolic or cardiovascular effects, which implies that some re-appraisal of adipokines role may need to take place. It still remains obscure whether the observed disturbances in various adipokine systems in subjects with connective tissue diseases contribute to their development or only reflect the presence or activity of inflammatory process, which itself is induced by other pro-inflammatory factors.

No previous study determined monocyte- and lymphocyte-suppressing effects of levothyroxine and selenomethionine and assessed whether their coadministration is superior to treatment with only one of these drugs. Our objective was to compare the effect of levothyroxine and selenomethionine on monocyte and lymphocyte cytokine release and systemic inflammation in patients with Hashimoto's thyroiditis. We conducted a randomized clinical trial involving a group of 170 ambulatory euthyroid women with recently diagnosed and previously untreated Hashimoto's thyroiditis and 41 matched healthy subjects. Participants were randomized in a double-blind fashion to receive a 6-month treatment with levothyroxine, selenomethionine, levothyroxine plus selenomethionine, or placebo. One hundred sixty-five patients completed the study. Monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein (CRP) were assessed. Compared with the control subjects, monocytes and lymphocytes of Hashimoto's thyroiditis patients released greater amounts of all cytokines studied. Levothyroxine reduced monocyte release of TNF-α, IL-1β, IL-6, and monocyte chemoattractant protein-1, whereas selenomethionine inhibited lymphocyte release of IL-2, interferon-γ, and TNF-α, which was accompanied by a reduction in plasma CRP levels. The decrease in cytokine release and in plasma CRP levels was strongest when both drugs were given together. Despite affecting different types of inflammatory cells, levothyroxine and selenomethionine exhibit a similar systemic antiinflammatory effect in euthyroid females with Hashimoto's thyroiditis. This action, which correlates with a reduction in thyroid peroxidase antibody titers, may be associated with clinical benefits in the prevention and management of Hashimoto's thyroiditis, particularly in subjects receiving both agents.

Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.