Berberine Inhibits the gene Expression and Production of Proinflammatory Cytokines by Mononuclear cells in Rheumatoid Arthritis and Healthy Individuals

Objective: Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis. Berberine is an alkaloid isolated from Berberis vulgaris and its anti-inflammatory effect has been identified. Method: Twenty newly diagnosed RA patients and 20 healthy controls participated. Peripheral mononuclear cells were prepared and stimulated with bacterial lipopolysachharide (LPS,1 µg/ml), exposed to different concentrations of berberine (10 and 50µM) and dexamethasone (10-7 M) as a reference. Toxicity of compounds was evaluated by WST-1 assay. Expression of TNF-α and IL-1β were determined by quantitative real-time PCR. Protein level of secreted TNF-α and IL1β were measured by using ELISA. Result: Berberine did not have any toxic effect on cells, whereas Lipopolysachharide (LPS) stimulation caused a noticeable rise in TNF-α and IL-1β production. Berberine markedly downregulated the expression of both TNF-α and IL1β and inhibits TNF-α and IL-1β secretion from LPS-stimulated PBMCs. Discussion: This study provided molecular basis for anti-inflammatory effect of berberine on human mononuclear cells through the suppression of TNF-a and IL-1secretion. Our findings highlighted the significant inhibitory effect of berberine on proinflammatory responses of mononuclear cells from rheumatoid arthritis individuals, which may be responsible for antiinflammatory property of Barberry. We observed that berberine at high concentration exhibited anti-inflammatory effect in PBMCs of both healthy and patient groups by suppression of TNF-a and IL-1cytokines at both mRNA and protein levels. Conclusions: Berberine may inhibit the gene expression and production of pro-inflammatory cytokines by mononuclear cells in rheumatoid arthritis and healthy individuals without affecting cells viability. Future studies with larger sample size is needed to prove the idea.

Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells

Newborns and infants are highly susceptible to viral and bacterial infections, but the underlying mechanism remains poorly understood. We show that neonatal B cells effectively control the production of proinflammatory cytokines by both neonatal plasmacytoid and conventional dendritic cells, in an interleukin (IL) 10–dependent manner, after Toll-like receptor (TLR) 9 triggering. This antiinflammatory property of neonatal B cells may extend to other TLR agonists (Pam3CSK4, lipopolysaccharide, and R848) and viruses. In the absence of B cells or of CD5+ B cell subsets, neonatal mice developed stronger inflammatory responses and became lethally susceptible to CpG challenge after galactosamine sensitization, whereas wild-type (WT) mice were resistant. Paradoxically, interferon (IFN)-α/β enhanced the inflammatory response to CpG challenge in adult mice, whereas they helped to control neonatal acute inflammation by stimulating the secretion of IL-10 by neonatal B cells. Finally, WT neonatal B cells rescued IL-10−/− neonates from a lethal CpG challenge, whereas IFN-α/β receptor–deficient B cells did not. Our results show that type I IFNs support a negative regulatory role of neonatal B cells on TLR-mediated inflammation, with important implications for neonatal inflammation and infection.

COMPARATIVE EFFECTS OF CORTICOSTEROIDS ON HOST RESISTANCE TO INFECTION IN RELATION TO CHEMICAL STRUCTURE

In a comparative study concerning the effect of corticosteroids on host resistance to infections, five compounds were found to decrease host resistance, while three did not have this property, although all eight compounds were highly antiinflammatory. The compounds capable of decreasing host resistance were (I) hydrocortisone acetate; (III) 9α-fluoro, 16α-methylprednisolone acetate; (IV) 9α-fluoro, 16α-hydroxyprednisolone; (V) 9α-fluoro, 16α-hydroxyprednisolone, 16α–17α-acetonide; and (VII) 9α-fluoro, 16α-hydroxypredmsolone, 16α-, 17α-acetonide, 21 disodium phosphate. Following a single injection of 10 mg of any of these compounds, latent corynebacterial infection was provoked into active pseudotuberculosis. Also, mice injected with these corticosteroids were more susceptible to infection with Corynebacterium kutscheri, Staphylococcus aureus, Klebsiella pneumoniae, or Listeria monocytogenes. These same corticosteroids inhibited the ability of mouse peritoneal macrophages to spread on glass surfaces. The three compounds incapable of decreasing host resistance, although highly antiinflammatory, were: (II) 6α-methylprednisolone, 21 sodium hemisuccinate: (VI) 9α-fluoro, 16α-hydroxyprednisolone, 16α-, 17α-acetonide, 21 hemisuccinate; and (VIII) 9α-fluoro, 16α-hydroxyprednisolone, 16, 21 dihemisuccinate. These three compounds were also unable to inhibit the spreading of macrophages on glass. The importance of succinate group bound to the corticosteroid molecule as hemisuccinate is emphasized since it is seen that the infection-provoking property can be dissociated from the antiinflammatory property. This finding may be of practical consequence in selecting a corticosteroid for treatment in disease, and also shows that one cannot use, indifferently, corticosteroids only on the basis of their common antiinflammatory property.