Acta vet. scand. 2002, 43, 165-171. Immune-Mediated Fever in the Dog. Occurrence of Antinuclear Antibodies, Rheumatoid Factor, Tumor Necrosis Factor and Interleukin-6 in Serum By J. Øvrebø Bohnhorst1, I. Hanssen2 and Torolf Moen1 1Department of Immunology and Transfusion Medicine, University Hospital of Trondheim, and 2Strinda Small Animal Clinic, Trondheim, Norway. Øvrebø Bohnhorst J, Hanssen I, Moen T: Immune-mediated fever in the dog. Oc- currence of antinuclear antibodies, rheumatoid factor, tumor necrosis factor and interleukin-6 in serum. Acta vet. scand. 2002, 43, 165-171. – Contents of antinuclear antibodies (ANA), rheumatoid factor (RF), tumor necrosis factor (TNF-α) and inter- leukin-6 (IL-6) were measured in serum from 20 dogs with immune-mediated fever. Seven out of 20 patients were ANA positive, 1 out of 20 was positive to antibodies against extractable nuclear antigens (ENA), 1 out of 20 was positive to antibodies against deoxynucleoproteins (DNP), 2 out of 13 were RF positive and none out of 20 pa- tients had antibodies against native DNA in the serum. TNF-α was not detected in any serum of 15 dogs with immune-mediated fever, while 10 out of 13 presented with ele- vated IL-6. The results varied between patients, but the IL-6 level was high in most of them. This indicate a role for IL-6 in the pathogenesis of immune-mediated fever in most cases. dog; immune; fever; antinuclear antibodies; rheumatoid factor; tumor necrosis factor; interleukin-6. Introduction Fever of unknown origin (FUO) is not an un- common problem in clinical canine medicine. In human medicine the criteria which deﬁne FUO are (1) prolonged fever of more than 3 weeks duration associated with non-speciﬁc signs of illness such as lethargy, anorexia and weight loss, (2) temperature at least 0.83 °C above normal on several occasions and (3) di- agnosis still uncertain after one week of hospi- talization and routine laboratory tests (Peters- dorf & Beeson 1961,Vickery & Quinnell 1977, Wolf & Dinarello 1979). These criteria are not directly applicable to ca- nine medicine, but may serve as useful guide- lines to exclude fever of shorter duration asso- ciated with infections. The deﬁnition of FUO in dogs was expanded by Dunn & Dunn 1998 to include dogs with temperature in excess of 40 °C on more than one occasion. In humans the relative frequencies of causes of FUO are well established (Petersdorf & Beeson 1961, Jacoby & Swartz 1973), with the cases being devided as follows: infection 40%, neo- plasia 20%, immune-mediated 15%, miscella- neous 20% and 5% remaining undiagnosed. In canine medicine the relative frequency of different causes of FUO varies between studies. The distribution suggested by Feldman (1980) was infections 40%, neoplasia 20%, immune- mediated disease 20%, miscellaneous condi- tions 10% and undiagnosed (true FUO) 10%. Bennet (1995) claimed that infection is ac- Acta vet. scand. vol. 43 no. 3, 2002