Activity of locus coeruleus (LC) neurons, the major noradrenergic cell-body group in the brain whose axons give rise to approximately 70% of norepinephrine (NE) in the brain, is believed to play an important role in attention/vigilance, cognitive functions and behavioral disorders, particularly depression. Results described here show that in the rat, intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, a bacterial endotoxin) causes long-lasting changes in electrophysiological activity of LC neurons that are mediated by interleukin-1 (IL-1) acting locally in the LC region. First, it was found that IL-1, when microinjected into the LC region or stimulated/expressed in that brain region, increased activity of LC neurons. The only exception to this was that a very low dose of microinjected IL-1 (5 pg) decreased LC activity, which could be blocked by an antagonist to corticotropin-releasing hormone (CRH), thus suggesting that the decrease was due to IL-1 stimulation of CRH release. All of these effects could be blocked by injection and/or infusion of IL-1 receptor antagonist (IL-1RA) specifically into the LC region. Next, intraperitoneal (i.p.) injection of a low dose of LPS(10 µg/kg or 100 ng/kg) was also found to increase LC activity. The excitation of LC produced by 10 µg/kg i.p. LPS increased progressively for at least 1 week, with LC neurons firing at more than twice their normal rate at 1 week after the i.p. LPS injection. Alteration of LC activity lasted for 3 weeks after a single i.p. injection of 10 µg/kg LPS. The effects of i.p. LPS on LC activity at any time after i.p. injection could be blocked by a brief microinfusion of IL-1RA into the LC region, thereby indicating that changes in LC activity seen after the i.p. LPS were caused by IL-1 acting in the LC region. Finally, i.p. injection of peptidoglycan, representing gram-positive bacteria, and polyinsinic-polycytidylic acid [poly(I):(C)], representing viral infection, also caused increases in LC activity, and the effects of peptidoglycan [but not those of poly(I):(C)] were blocked by microinfusion of IL-1RA into LC. These findings suggest that bacterial infections can give rise to prolonged changes in brain activity through cytokine action in brain.

There is a growing body of evidence to suggest direct involvement of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in the initiation of skeletal muscle catabolism and depressions in growth performance as a result of diseases, while TNF-α and IL-6 are presumably under the control of IL-1. An experiment was conducted to investigate whether an interleukin-1 receptor antagonist (IL-1ra) could reduce growth depressions in a model of subclinical disease in growing pigs. In this study, 24 crossbred barrows and gilts were randomly assigned to three treatments: (1) healthy control (HC), saline infusion; (2) sick control (SC), infection with Mycoplasma hyopneumoniae and vaccination with porcine reproductive and respiratory syndrome modified live virus (PRRSV) vaccine and saline infusion; (3) SC plus infusion with IL-1ra (SC+IL-1ra). An additional six pigs were killed at the initiation of the trial to determine initial body composition for estimation of carcass nutrient retention rates. During the 28-day experimental period, the SC pigs had growth performance similar to that of the HC pigs and the highest levels of plasma cytokines (P<0·10). The SC+IL-1ra pigs had growth performance similar to the HC pigs, but the SC+Il-1ra pigs tended to have higher growth rates than the SC pigs (P<0·10), the highest carcass protein accretion rate (P<0·10) and similar levels of plasma cytokines compared with the HC pigs. Plasma levels of insulin-like growth factor-1 (IGF-1) on day 22 tended to be higher (P<0·10) in the HC pigs compared with the SC or SC+IL-1ra pigs and treatment×sex interaction was observed on day 29; the IGF-1 levels tended to be higher in SC+IL-1ra gilts and SC barrows (P<0·10). These results indicate that infusion with IL-1ra in a model of subclinical disease helps attenuate the catabolic effects of immune system stimulation.

Interactions between nutrition and immunity are diverse and have profound implications on animal growth and productivity. The innate immune system provides protection during the initial stages of infection and is responsible for mediating many of the alterations in nutrient metabolism. The macrophage is the key sensory and regulatory cell of the innate immune system. Their pro-inflammatory cytokines coordinate local immunity to pathogens, yet also act systemically to alter metabolic homeostasis and decrease food intake and growth rate. Altered energy, amino acid, lipid, and mineral metabolism have nutritionally important implications. For example, an innate immune response results in decreased uptake of amino acids by skeletal muscles and a corresponding increase in uptake by the liver and to a lesser extent by leukocytes. The net result is a decrease in amino acid requirements with no change in the efficiency of their use for growth. The shift in the priority of individual tissues for nutrients appears to be accomplished by changes in the types and amounts of their nutrient transporters and storage proteins. Adaptive immune responses result in considerably more subtle changes in nutrient metabolism than innate responses.

Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated β-galactosidase activity and accelerate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-α or IL-1α transiently increases the production of reactive oxygen species (ROS) in human fibroblasts. Here we propose that repeated stimulation of WI-38 fibroblasts with TNF-α or IL-1α can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positive for senescence associated β-galactosidase activity. The involvement of ROS is suggested by experiments where the stimulation of fibroblasts with TNF-α or IL-1α are performed in the presence of N-acetylcysteine which increases the intracellular antioxidant potential. It is proposed that the decrease in the proportions of morphotypes I and II, and the increase in the proportions of morphotypes III to VI observed after successive stimulation with TNF-α or IL1-α is attributed to an increased ROS production occurring during the stimulation.