Pfliigers Arch (1992) 421:299-301
Journal of Physiology 9 Springer-Verlag 1992"
Fever responses in newborn lambs K. Goelst, D. Mitchell, and H. Laburn Department of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown 2193, South Africa Received January 10, 1992/Received after revision March 16, 1992/Accepted March 19, 1992
Abstract. Neonatal lambs failed to respond with an increase in b o d y temperature to i.v. injection o f b o t h endotoxin (0.4 ~tg/kg), a Gram-negative bacterial pyrogen, and the cell walls o f S t a p h y l o c o c c u s a u r e u s (1 • 109), a Gram-positive bacterial pyrogen. However, the fall in ser u m iron concentration that n o r m a l l y accompanies injection o f b o t h the pyrogens in adults was not attenuated in the neonates. We believe that the central nervous system origin o f the fever pathway is suppressed in neonatal lambs.
Key words: Fever - N e o n a t e - Sheep
Introduction H u m a n neonates, until they are a b o u t a week old, m a y fail to develop fever during infection [5]. N e w b o r n lambs [4], guinea-pigs [15], and rabbits [14] also have attenuated fever responses when injected with pyrogens, including bacterial endotoxin, endogenous pyrogen [2] and prostaglandin [13]. The m e c h a n i s m o f the attenuation o f the temperature response to infection has not been established [4, 16]. Current possibilities include an inability o f leucocytes to m a n u f a c t u r e interleukin-1 (IL-I) [9], immaturity o f the t h e r m o r e g u l a t o r y effector mechanisms responsible for raising b o d y temperature [14] or the presence o f an endogenous antipyretic [17, 4]. We have tried to elucidate the m e c h a n i s m o f the attenu a t i o n o f fever in n e w b o r n lambs by measuring two separate c o m p o n e n t s o f the fever s y n d r o m e [8], namely b o d y temperature and serum iron status, following i.v. injection o f two distinct pyrogens, Gram-negative endotoxin and Gram-positive S t a p h y l o c o c c u s a u r e u s cell wails.
Correspondence to: K. Goelst
Materials and methods Sixteen lambs (3.9+0.7 kg, mean+SD), born to time-mated Dorper ewes, were used. All the ewes lambed spontaneously. The lambs remained in their pens with their mothers and were unrestrained throughout the experiments. The animals were kept on a natural day/night cycle at an ambient temperature of 20+ 1 ~ Body temperatures were measured with in-dwelling copper/constantan thermocouples, inserted about 100 mm into the rectum, for at least 1 h before and 4 h after injection. The thermocouple was held in place until the output, as displayed on the electroulc thermometer (Bat-12, Sensortek, Clifton, N;J., USA), was stable. Four-hour fever indices were calculated as the time integral of the body temperature elevation above the temperature prior to injection (~ All injections were made into a jugular vein and at the same time each day (0900 hours). Six lambs were given 1 x 109 S. aureus cell walls (Calbiochem, San Diego, Calif., USA), 5 lambs 0.4 I~g/kg endotoxin from Salmonella typhosa (Difco, West Molesey, Surrey, England) and the remaining 5 lambs sterile saline, within 24 h of birth (day 1), and 4 days and again 5 weeks after birth. Blood samples (4 ml) taken from a jugular vein, 1 h before (0800 hours) and 6 h after (1500 hours) the pyrogen injections, were used to measure serum iron levels. The procedure for serum iron determination was based on the recommendations of the International Committee for Standardization in Haematology (1978). The results were subjected to the Student-Newman-Keuls (SNK) test for multiple comparison [6] and values of P
Journal of Physiology 9 Springer-Verlag 1992"
Fever responses in newborn lambs K. Goelst, D. Mitchell, and H. Laburn Department of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown 2193, South Africa Received January 10, 1992/Received after revision March 16, 1992/Accepted March 19, 1992
Abstract. Neonatal lambs failed to respond with an increase in b o d y temperature to i.v. injection o f b o t h endotoxin (0.4 ~tg/kg), a Gram-negative bacterial pyrogen, and the cell walls o f S t a p h y l o c o c c u s a u r e u s (1 • 109), a Gram-positive bacterial pyrogen. However, the fall in ser u m iron concentration that n o r m a l l y accompanies injection o f b o t h the pyrogens in adults was not attenuated in the neonates. We believe that the central nervous system origin o f the fever pathway is suppressed in neonatal lambs.
Key words: Fever - N e o n a t e - Sheep
Introduction H u m a n neonates, until they are a b o u t a week old, m a y fail to develop fever during infection [5]. N e w b o r n lambs [4], guinea-pigs [15], and rabbits [14] also have attenuated fever responses when injected with pyrogens, including bacterial endotoxin, endogenous pyrogen [2] and prostaglandin [13]. The m e c h a n i s m o f the attenuation o f the temperature response to infection has not been established [4, 16]. Current possibilities include an inability o f leucocytes to m a n u f a c t u r e interleukin-1 (IL-I) [9], immaturity o f the t h e r m o r e g u l a t o r y effector mechanisms responsible for raising b o d y temperature [14] or the presence o f an endogenous antipyretic [17, 4]. We have tried to elucidate the m e c h a n i s m o f the attenu a t i o n o f fever in n e w b o r n lambs by measuring two separate c o m p o n e n t s o f the fever s y n d r o m e [8], namely b o d y temperature and serum iron status, following i.v. injection o f two distinct pyrogens, Gram-negative endotoxin and Gram-positive S t a p h y l o c o c c u s a u r e u s cell wails.
Correspondence to: K. Goelst
Materials and methods Sixteen lambs (3.9+0.7 kg, mean+SD), born to time-mated Dorper ewes, were used. All the ewes lambed spontaneously. The lambs remained in their pens with their mothers and were unrestrained throughout the experiments. The animals were kept on a natural day/night cycle at an ambient temperature of 20+ 1 ~ Body temperatures were measured with in-dwelling copper/constantan thermocouples, inserted about 100 mm into the rectum, for at least 1 h before and 4 h after injection. The thermocouple was held in place until the output, as displayed on the electroulc thermometer (Bat-12, Sensortek, Clifton, N;J., USA), was stable. Four-hour fever indices were calculated as the time integral of the body temperature elevation above the temperature prior to injection (~ All injections were made into a jugular vein and at the same time each day (0900 hours). Six lambs were given 1 x 109 S. aureus cell walls (Calbiochem, San Diego, Calif., USA), 5 lambs 0.4 I~g/kg endotoxin from Salmonella typhosa (Difco, West Molesey, Surrey, England) and the remaining 5 lambs sterile saline, within 24 h of birth (day 1), and 4 days and again 5 weeks after birth. Blood samples (4 ml) taken from a jugular vein, 1 h before (0800 hours) and 6 h after (1500 hours) the pyrogen injections, were used to measure serum iron levels. The procedure for serum iron determination was based on the recommendations of the International Committee for Standardization in Haematology (1978). The results were subjected to the Student-Newman-Keuls (SNK) test for multiple comparison [6] and values of P
