Insulin‐like growth factor‐I and the liver

Insulin‐like growth factors (IGFs) play an essential role in growth and development, as well as in the overall cellular regulation and metabolism in the human body. In chronic liver disease, IGF levels are decreased, and the circulating levels correlate to the extent of hepatocellular dysfunction. Patients with cirrhosis are characterised by a variety of metabolic disturbances, including nutritional and metabolic complications such as insulin resistance, malnutrition, osteopenia and hypogonadism, all related to IGF‐I deficiency. The complex process of hepatic fibrogenesis and the systemic consequences in cirrhosis are only partly understood. Disruption of the growth hormone (GH)–IGF‐I axis seems to be closely associated with the development of liver disease, and treatment with recombinant human IGF (rhIGF)‐I has been shown to halt, and even reverse, the fibrotic degeneration. IGF‐I in itself has a strong antifibrotic effect that acts directly through the GH/IGF system and indirectly by the regulation of hepatoprotective and profibrogenic factors. It is most likely that IGF‐I deficiency contributes to the diverse metabolic complications of cirrhosis. At present, liver transplantation remains the only efficient treatment of cirrhosis, and thus new methods of managing the disease are called for. RhIGF‐I supplementation and IGF‐I gene therapy may represent future perspectives of treatment.     

Extended indications for anti‐tumor necrosis factor‐α therapy

Tumour necrosis factor‐α is a pleiotropic cytokine which has a broad range of actions in inflammation, infection and immunity. TNF‐α is supposed to play a crucial role in the pathogenesis of various autoimmune diseases. TNF‐α blocking agents have been demonstrated to be highly effective in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. TNF‐α inhibitors also have been tried with other rheumatic diseases and have emerged as promising treatments. We here review the current evidences of effectiveness of the anti‐TNF‐α therapy in various autoimmune diseases.     

Granulocyte colony‐stimulating factor‐producing lung cancer and acute respiratory distress syndrome

Granulocyte colony‐stimulating factor (G‐CSF)‐producing lung cancers are known to cause extreme leukocytosis. However, acute respiratory distress syndrome (ARDS) caused by G‐CSF‐producing lung cancer is extremely rare. We present a case of G‐CSF‐producing lung cancer with marked leukocytosis, which rapidly led to severe ARDS after the patient developed pneumonia. The present case suggests that extreme leukocytosis may easily lead to ARDS, triggered by infection. Thus, G‐CSF‐producing lung cancer with marked leukocytosis should be carefully monitored before surgery and during treatment.     

Experience with anti‐tumor necrosis factor‐α therapy in India

Aims: To review the Indian experience with anti‐tumor necrosis factor (TNF)‐α therapy. Methods: ‘PubMed’ and ‘IndMED’ were searched for Indian studies on anti‐TNF‐α therapy. Data were compiled and analysed. Results: Data on infliximab from 176 patients from five different series were collated. One hundred and forty‐seven had ankylosing spondylitis (AS), nine had polyarticular juvenile idiopathic arthritis (JIA), 12 had rheumatoid arthritis (RA), six had undifferentiated spondyloarthropathy, one had inflammatory bowel disease‐related spondyloarthritis and one had psoriatic arthritis. Thus, 155/176. (88%) had spondyloarthropathy (SpA). No screening for latent tuberculosis was done in any of the studies. One series comprising 108 cases of AS, used 3 mg/kg infliximab infusions (instead of 5 mg/kg) at 8‐weekly intervals with omission of the 2‐week and 6‐week doses. All others with SpA (n = 47) followed the standard protocol: 171/176 patients had a significant improvement. Reactivation tuberculosis developed in 5/47 (10.6%) SpA patients treated with standard doses of infliximab. This amounted to 56 times increased risk compared to baseline (0.187%). None of the 129 patients treated with 3 mg/kg infusions of infliximab developed reactivation tuberculosis (AS ?108, RA ?12, JIA ?9). The lone study on etanercept showed good efficacy in 40 patients with RA. However, seven serious adverse events occurred. Conclusions: Infliximab showed expected efficacy in SpA, RA and JIA. Reactivation tuberculosis developed in 10.6% of the SpA group treated with standard regimen. Patients treated with lower doses of infliximab which included a large subgroup of SpA patients and those with RA or JIA did not develop tuberculosis.     

Stromal‐derived factor‐1 gene variations in pediatric patients with primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) of childhood is an autoimmune disease characterized by abnormally increased destruction of platelets and decreased megakaryopoiesis. Stromal‐derived factor‐1 (SDF‐1) plays a role in megakaryopoiesis and may be involved in the pathogenesis of ITP. Five single nucleotide polymorphisms (SNPs) of the SDF‐1 gene, including rs1801157, rs2839693, rs2297630, rs1065297, and rs266085, were assessed in 100 children with ITP and 126 healthy controls. The genotypes were analyzed by tetra ARMS polymerase chain reaction and confirmed by direct sequencing. Compared with controls, the rs2839693 A/A and rs266085 C/T genotypes were decreased in ITP patients (P = 0.004 and 0.007, respectively). The odds ratios of the latter genotypes were 0.48, 95% CI 0.28–0.82. Further analysis of the relationship between SDF‐1 polymorphisms and clinical features showed that rs2297630 A/G was associated with protection from chronicity (P = 0.002; OR, 0.07; 95% CI, 0.01–0.61) and steroid dependence (P = 0.007; OR, 0.10; 95% CI, 0.01–0.84) in ITP patients. However, rs266085 genotype C/C was associated with risk of steroid dependence (P = 0.012, OR 3.87, 95% CI 1.27–11.77). The findings of this study suggest that SDF‐1 gene variations may be associated with the occurrence and prognosis of childhood ITP.     

Insulin‐like growth factor‐II: its role in metabolic and endocrine disease

Insulin‐like growth factor‐II (IGF‐II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF‐I. IGF‐II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF‐II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF‐II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.