Physiological effects of a novel immune stimulator drug, (1,4)-α-D-glucan, in rats.
The (1,4)-α-D-glucan (α-D-glucan), derived from medicinal plant, Tinospora cordifolia, activates human lymphocytes with downstream synthesis of the pro- and anti-inflammatory cytokines, in vitro. We investigated physiological and immunological effects of a low and a high dose of α-D-glucan (0.5 and 10 mg/kg), in vivo, testing the hypothesis that intravenous administration of α-D-glucan does not affect haemodynamic, respiratory, haematological, and immune responses in normal rats. Male rats (300-400 g) were anaesthetized, tracheostomized, and catheterized in one femoral artery and vein. The mean arterial blood pressure and heart rate were continuously recorded. The baselines for gas exchange, differential blood cell count, and plasma concentration of TNF-α, IL-1β, IL-4, IL-6, and IFN-γ were determined. Rats were then randomly assigned to controls (n = 7), a low dose (0.5 mg/kg; n = 10), and a high dose (10 mg/kg; n = 7) of α-D-glucan for a six 6 hr study period. Gas exchange, differential cell count, plasma concentration of TNF-α, IL-1β, IL-4, IL-6, and IFN-γ, and mean arterial blood pressure values remained within physiological range. Intravenous administration of 10 mg/kg α-D-glucan created tachycardia, associated with hyperventilation, and significant reductions in the blood haemoglobin and haematocrit concentrations. We suggest that these in vivo effects of α-D-glucan should be considered for future clinical and/or experimental trials.
Koppada
Ravishankar
R
Division of Critical Care Medicine, Miami Children's Hospital, Miami, FL, USA.
Norozian
Faraz M
FM
Torbati
Dan
D
Kalomiris
Sophia
S
Ramachandran
Cheppail
C
Totapally
Balagangadhar R
BR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005936:Glucans / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D010936:Plant Extracts; D051381:Rats; D017207:Rats, Sprague-Dawley; D031610:Tinospora / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D005936:Glucans; D053583:Interleukin-1beta; D015850:Interleukin-6; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; C040088:1,4-glucan