**Table 6.**

*P < 0.05.*

*Cytokine concentrations in dogs non-infected and dogs with Anaplasmataceae.*

**Figure 3.**

*Correlation between viscosity with erythrocytes, shear rates and IFN-γ; erythrocytes with shear rates and IFN-γ; and IFN-γ with shear rates of dogs infected with Anaplasmataceae.*

**37**

**4. Conclusion**

*Hemorheological Evaluation and Cytokine Production in Dogs Naturally Infected…*

in erythrocytes due to increased serum fibrinogen concentration [127].

Leishmania-positive dog samples, nor even a correlation between viscosity and immunoglobulins. However, it has been reported that fibrinogen binding may occur

Interestingly, in this work, the serum IFN-γ concentration was promising. Regarding the group of animals infected by bacteria of the Anaplasmataceae family, this interleukin showed a strong positive correlation with blood viscosity (p = 0.007; r = 0.73), negative correlation with shear rate (p = 0.016; r = −0.68), which may indicate a modulation of hemorheological behavior, mainly a decrease in blood viscosity and, consequently, an increase in shear rate in animals infected by

Cytokine immunomodulation is also reported in other mandatory intracellular

The possible correlation of IFN-γ with erythrocytes (p = 0.04; r = 0.6) in relation to the group of infected animals allows us to infer that IFN-γ was able to pathologically immunomodulate, aggravating the anemic condition in dogs. Martin et al. [61] described that IFN-γ is linked to the survival of the Anaplasmataceae infected patient, and this cytokine may have its effect increased in the presence of TNF-α [62]. No correlations were found between IFN-γ and TNF-α, even though there were serum concentrations of both cytokines in the blood of animals infected by bacteria from Anaplasmataceae family. Perhaps, TNF-α may influence the effect of IFN-γ on

parasite infections. Studies by Scherer et al. [7] demonstrated that in *P. vivax*infected patients, IL-17a was the cytokine responsible for decreasing blood viscosity, which probably decreased erythrocyte rupture, as these cells demonstrated easy

disease stage differences caused by Anaplasmataceae family bacteria in dogs.

Serum IL-10 levels showed a difference between the studied groups [**Table 6**], being relevant the increase of its concentration in dogs infected by Anaplasmataceae bacteria. Studies by Faria et al. [70] demonstrated that experimentally infected *E. canis* infected lymphocytes and splenocytes have high IL-10 and low IFN-γ production, indicating modulation to a Th2-like profile, as IL-10

Although IFN-γ is important in controlling infection with a Th1-type immune response [75], it can also be detrimental to erythrocytes in animals infected with Anaplasmataceae as it may lead to a severe decrease in cell count, if not immuno-

The use of IL-12 [11] and continuous use of IFN-γ [10] assist in the treatment of Leishmania infected animals, as the Th1 response profile is effective in eliminating the parasite. Experimental controlled use of anti-IL-10 antibodies also demonstrated improvement in Leishmania positive animals [128]. Thus, dogs undergoing treatment with Anaplasmataceae are likely to have a better chance of eliminating the agent using IFN-γ at controlled doses. In the case of dogs with anemia, perhaps the regulated use of IL-10 may immunomodulate the response and prevent the

Dogs naturally infected by Anaplasmataceae have serum concentration of different cytokines, but IFN-γ seems to be responsible for decreasing blood viscosity in these animals and causing disturbances in erythrocytes that are harmful. However, IFN-γ is also important in eliminating Anaplasmataceae by regulating the prolifera-

Alteration of blood rheology in dogs naturally infected with Anaplasmataceae probably occurs due to the systemic character of the infection that leads to erythrocyte alterations, which in turn disrupt the normal blood flow in these animals.

*DOI: http://dx.doi.org/10.5772/intechopen.91191*

bacteria of the Anaplasmataceae family.

osmotic shock due to infection.

regulated by another cytokine.

negatively modulates IFN-γ production.

deleterious action of IFN-γ on erythrocytes.

tion of these bacteria in infected dogs.

#### *Hemorheological Evaluation and Cytokine Production in Dogs Naturally Infected… DOI: http://dx.doi.org/10.5772/intechopen.91191*

Leishmania-positive dog samples, nor even a correlation between viscosity and immunoglobulins. However, it has been reported that fibrinogen binding may occur in erythrocytes due to increased serum fibrinogen concentration [127].

Interestingly, in this work, the serum IFN-γ concentration was promising. Regarding the group of animals infected by bacteria of the Anaplasmataceae family, this interleukin showed a strong positive correlation with blood viscosity (p = 0.007; r = 0.73), negative correlation with shear rate (p = 0.016; r = −0.68), which may indicate a modulation of hemorheological behavior, mainly a decrease in blood viscosity and, consequently, an increase in shear rate in animals infected by bacteria of the Anaplasmataceae family.

Cytokine immunomodulation is also reported in other mandatory intracellular parasite infections. Studies by Scherer et al. [7] demonstrated that in *P. vivax*infected patients, IL-17a was the cytokine responsible for decreasing blood viscosity, which probably decreased erythrocyte rupture, as these cells demonstrated easy osmotic shock due to infection.

The possible correlation of IFN-γ with erythrocytes (p = 0.04; r = 0.6) in relation to the group of infected animals allows us to infer that IFN-γ was able to pathologically immunomodulate, aggravating the anemic condition in dogs. Martin et al. [61] described that IFN-γ is linked to the survival of the Anaplasmataceae infected patient, and this cytokine may have its effect increased in the presence of TNF-α [62]. No correlations were found between IFN-γ and TNF-α, even though there were serum concentrations of both cytokines in the blood of animals infected by bacteria from Anaplasmataceae family. Perhaps, TNF-α may influence the effect of IFN-γ on disease stage differences caused by Anaplasmataceae family bacteria in dogs.

Although IFN-γ is important in controlling infection with a Th1-type immune response [75], it can also be detrimental to erythrocytes in animals infected with Anaplasmataceae as it may lead to a severe decrease in cell count, if not immunoregulated by another cytokine.

Serum IL-10 levels showed a difference between the studied groups [**Table 6**], being relevant the increase of its concentration in dogs infected by Anaplasmataceae bacteria. Studies by Faria et al. [70] demonstrated that experimentally infected *E. canis* infected lymphocytes and splenocytes have high IL-10 and low IFN-γ production, indicating modulation to a Th2-like profile, as IL-10 negatively modulates IFN-γ production.

The use of IL-12 [11] and continuous use of IFN-γ [10] assist in the treatment of Leishmania infected animals, as the Th1 response profile is effective in eliminating the parasite. Experimental controlled use of anti-IL-10 antibodies also demonstrated improvement in Leishmania positive animals [128]. Thus, dogs undergoing treatment with Anaplasmataceae are likely to have a better chance of eliminating the agent using IFN-γ at controlled doses. In the case of dogs with anemia, perhaps the regulated use of IL-10 may immunomodulate the response and prevent the deleterious action of IFN-γ on erythrocytes.
