Lowered tumor necrosis factor receptors, but not increased insulin sensitivity, with infliximab.
OBJECTIVE
To verify whether Infliximab could modify insulin sensitivity and TNF-alpha and GLUT4 mRNA expression in muscle and adipose tissue of morbidly obese subjects. Soluble TNF receptors I and II (TNFR-I and TNFR-II) were also assayed.


METHODS
Six obese subjects were investigated before and 2 weeks after a single intravenous administration of 5 mg/kg Infliximab; insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp, and TNF-alpha and GLUT4 mRNA expression were assessed by reverse-transcriptase polymerase chain reaction on muscle and adipose tissue. TNF-alpha, TNFR-I, and TNFR-II were determined using the ELISA technique.


RESULTS
Infliximab infusion did not affect fasting plasma insulin or fasting plasma glucose levels; whole body glucose uptake did not change significantly. TNF-alpha and GLUT4 mRNA did not show any significant change in muscle or adipose tissue. Serum TNF-alpha was undetectable before and after treatment, whereas TNFR-I and TNFR-II concentrations significantly decreased (p < 0.01).


CONCLUSIONS
An explanation for the absence of effect of Infliximab on insulin resistance in morbidly obese subjects may be the paracrine way of action of this cytokine. Because Infliximab is predominantly distributed within the vascular compartment, its effectiveness in penetrating muscle and adipose tissue is potentially low. The significant decrease of TNFR-I and TNFR-II might be ascribed to a targeted effect of Infliximab on the immune system.
Di Rocco
Paola
P
Institute of Internal Medicine, Catholic University of Sacred Heart, Rome, Italy. paola_dirocco@hotmail.com
Manco
Melania
M
Rosa
Giuseppina
G
Greco
Aldo V
AV
Mingrone
Geltrude
G
D000273:Adipose Tissue / Q000737:chemistry; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015703:Antigens, CD / Q000097:blood*; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D005215:Fasting; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D006801:Humans; D007109:Immunity / Q000187:drug effects; D000069285:Infliximab; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity / Q000097:blood* / Q000378:metabolism / Q000628:therapy; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C495692:SLC2A4 protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab